Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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GENETIC LOCI ASSOCIATED WITH INCREASED FERTILITY IN MAIZE
FIELD OF THE INVENTION
The present invention relates to compositions and methods for identifying,
selecting
and producing maize plants having increased fertility.
BACKGROUND
Vip3 proteins have been successfully expressed in transgenic plants such as
maize and
cotton. For example, hybrid transgenic maize plants can express Vip3A proteins
at levels
which are insecticidal to pest insects and which have no negative impact on
the plant
phenotype. Thus, the Vip3A trait protects yield and yield potential of hybrid
maize plants.
However, Vip3 has been observed to cause decreased male fertility in certain
inbred maize
plants under normal growing conditions. This phenomenon is more prominent in
inbred
maize plants that are homozygous for a vip3A transgene. The degree to which
male fertility is
decreased is inbred specific - some inbreds exhibit little or no reduction in
male fertility when
homozygous for a v43 gene, other inbreds are somewhat sensitive to Vip3 and
exhibit a
significant reduction in male fertility when homozygous for a vip3 gene, and
other inbreds
are highly sensitive to Vip3 and exhibit exit emely low or no male
fertility when homozygous
for a v1p3 gene. The degree to which male fertility is decreased is also
affected by
environmental factors, such as water availability and temperature. In Vip3-
induced
reductions in male fertility, drought and high temperature conditions
exacerbate the the
reduction in male fertility; however, cooler growth conditions have been shown
to mitigate
the negative effects of Vip3 expression on male fertility.
Identifying genetic loci that enhance the fertility of maize plants expressing
a vip3
transgene could lead to more efficient crop production by allowing for the
identification,
selection and production of vip3-expressing inbred maize plants with increased
male fertility.
SUMMARY OF THE CLAIMED INVENTION
The present invention provides maize plants having increased male fertility,
as well as
compositions and methods for identifying, selecting and producing such plants.
In some embodiments, methods of identifying a maize plant or plant part having
one
or more characteristics associated with increased male fertility are provided.
Such methods
may comprise detecting, in a maize plant or plant part, a marker associated
with increased
male fertility.
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In some embodiments, methods of producing a maize plant having one or more
characteristics associated with increased male fertility are provided. Such
methods may
comprise detecting, in a maize plant part, the presence of a marker associated
with increased
male fertility and producing a maize plant from said maize plant part. Such
methods may
further comprise introducing the marker into said maize plant part.
In some embodiments, breeding methods are provided. Such methods may comprise
detecting, in a maize plant or plant part, the presence of a marker associated
with increased
male fertility (e.g., in nucleic acid, for example, in an amplification
product from a nucleic
acid sample from the plant or plant part) and selecting said maize plant or
plant part for
breeding. In embodiments, the method may further comprise crossing the maize
plant (or an
ancestor, progeny or sibling thereof) with a second maize plant that
optionally lacks the
marker to produce a progeny maize plant, which optionally comprises the
marker.
Still further, the invention provides a method for producing a plant having
one or
more characteristics associated with increased male fertility, comprising:
selecting from a
diverse maize plant population a maize plant comprising a marker associated
with increased
male fertility as described herein; and crossing the maize plant (or an
ancestor, progeny or
sibling thereof) with itself or a second maize plant to produce a progeny
plant comprising the
marker, thereby producing a plant having one or more characteristics
associated with
increased male fertility. In embodiments, the second maize plant does not
comprise the
marker. In embodiments, the marker is detected in nucleic acid from the first
maize plant
and/or progeny plant (e.g., in an amplification product from a nucleic acid
sample from the
maize plant and/or progeny).
In some embodiments, methods of reducing costs associated with breeding and/or
seed production are provided. Such methods may comprise detecting, in a maize
plant or
plant part, the presence of a marker associated with increased male fertility
and selecting said
maize plant or plant part for breeding.
In some embodiments, methods of predicting male fertility are provided. Such
methods may comprise detecting, in a maize plant or plant part, the presence
of a marker
associated with increased male fertility (e.g., in nucleic acid from the plant
or plant part),
wherein the presence of the marker predicts a likelihood of increased male
fertility.
In some embodiments, methods of identifying a maize plant or plant part
comprising
at least one allele associated with increased male fertility are provided.
Such methods may
comprise detecting, in a maize plant or plant part (e.g., in nucleic acid from
the plant or plant
part), a marker associated with increased male fertility.
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In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise introducing a nucleic acid comprising at least one allele associated
with increased
male fertility into the genome of a maize plant part and producing a maize
plant from said
maize plant part. Such methods may further comprise detecting a marker
associated with
increased male fertility and/or the allele associated with increased male
fertility in nucleic
acid (e.g., in a nucleic acid sample) from said maize plant or plant part. In
embodiments, the
marker and/or allele is detected in an amplification product from a nucleic
acid sample from
said maize plant or plant part.
In some embodiments, methods of improving pollen production are provided. Such
methods may comprise introducing a nucleic acid comprising at least one allele
associated
with increased pollen production into the genome of a maize plant part and
producing a
maize plant from said maize plant part. Such methods may further comprise
detecting a
marker associated with increased pollen production and/or the allele
associated with
increased pollen production in nucleic acid (e.g., a nucleic acid sample) from
said maize plant
part. In embodiments, the marker is detected in an amplification product from
a nucleic acid
sample from said plant or plant part.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise introducing a genomic region associated with increased male fertility
into the
genome of a maize plant part and producing a maize plant from said maize plant
part. Such
methods may further comprise detecting a marker associated with increased male
fertility
and/or the genomic region associated with increased male fertility in nucleic
acid (e.g., a
nucleic acid sample) from said maize plant part. In embodiments, the marker is
detected in
an amplification product from a nucleic acid sample from the maize plant or
plant part.
In some embodiments, methods of improving pollen production are provided. Such
methods may comprise, consist essentially of or consist of introducing a
genomic region
associated with increased pollen production into the genome of a maize plant
part and
producing a maize plant from said maize plant part. Such methods may further
comprise
detecting a marker associated with increased pollen production and/or the
genomic region
associated with increased pollen production in nucleic acid (e.g., a nucleic
acid sample) from
said maize plant part. In embodiments, the marker is detected in an
amplification product
from a nucleic acid sample from the maize plant or plant part.
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In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise introducing a genomic region comprising one or more transgenes
associated with
increased male fertility into the genome of a maize plant or plant part.
In some embodiments, methods of improving pollen production are provided. Such
methods may comprise introducing a genomic region associated with increased
pollen
production into the genome of a maize plant or plant part and producing a
maize plant from
said maize plant part.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part to
produce a progeny maize plant or plant part, wherein said first maize plant or
plant part
comprises within its genome a marker associated with increased male fertility,
optionally
wherein said second maize plant or plant part lacks said marker, and wherein
said progeny
maize plant or plant part has said marker within its genome. Such methods may
further
comprise selecting said progeny plant based upon the presence of said marker.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part to
produce a progeny maize plant or plant part, wherein said first maize plant or
plant part
comprises within its genome an allele associated with increased male
fertility, optionally
wherein said second maize plant or plant part lacks said allele, and wherein
said progeny
maize plant or plant part has said allele within its genome. Such methods may
further
comprise selecting said progeny plant based upon the presence of said allele
and/or the
presence of a marker linked to said allele.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part to
produce a progeny maize plant or plant part, wherein said first maize plant or
plant part
comprises within its genome a genomic region comprising one or more transgenes
associated
with increased male fertility, optionally wherein said second maize plant or
plant part lacks
said genomic region, and wherein said progeny maize plant or plant part has
said genomic
region within its genome. Such methods may further comprise selecting said
progeny plant
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based upon the presence of said genomic region and/or the presence of a marker
linked to
said genomic region.
In some embodiments, methods of selecting a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part,
wherein the first maize plant or plant part comprises a marker associated with
increaced male
fertility and optionally wherein said second maize plant or plant part lacks
said marker, and
selecting a progeny plant or plant part that possesses said marker.
In some embodiments, methods of selecting a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part,
wherein the first maize plant or plant part comprises an allele associated
with increased male
fertility and optionally wherein said second maize plant or plant part lacks
said allele, and
selecting a progeny plant or plant part that possesses said allele and/or a
marker linked to said
allele.
In some embodiments, methods of selecting a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a first maize plant or plant part with a second maize plant
or plant part,
wherein the first maize plant or plant part comprises a genomic region
comprising one or
more transgenes associated with increased male fertility and optionally
wherein said second
maize plant or plant part lacks said genomic region, and selecting a progeny
plant or plant
part that possesses said genomic region and/or a marker linked to said genomic
region.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a donor maize plant or plant part with a recurrent maize
plant or plant part
and backcrossing progeny with said recurrent maize plants or plant part for
one or more
generations, wherein said donor maize plant or plant part comprises within its
genome a
marker associated with increased male fertility, wherein said recurrent maize
plant or plant
part optionally lacks said marker, and wherein at least one generation of said
progeny are
identified and/or selected for backcrossing by detecting the presence of said
marker.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a donor maize plant or plant part with a recurrent maize
plant or plant part
and backcrossing progeny with said recurrent maize plants or plant part for
one or more
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generations, wherein said donor maize plant or plant part comprises within its
genome an
allele associated with increased male fertility, wherein said recurrent maize
plant or plant part
optionally lacks said allele, and wherein at least one generation of said
progeny are identified
and/or selected for backcrossing by detecting the presence of said allele
and/or the presence
of a marker linked to said allele.
In some embodiments, methods of producing a maize plant or plant part having
one or
more characteristics associated with increased male fertility are provided.
Such methods may
comprise crossing a donor maize plant or plant part with a recurrent maize
plant or plant part
and backcrossing progeny with said recurrent maize plants or plant part for
one or more
generations, wherein said donor maize plant or plant part comprises within its
genome a
genomic region comprising one or more transgenes associated with increased
male fertility,
wherein said recurrent maize plant or plant part optionally lacks said
genomic, and wherein at
least one generation of said progeny are identified and/or selected for
backcrossing by
detecting the presence of said genomic region and/or the presence of a marker
linked to said
genomic region.
In embodiments, the invention also provides methods of improving seed
production
from a maize plant. To illustrate, in representative embodiments, the
invention provides a
method of improving seed production from a maize plant, comprising: crossing a
first maize
plant with a second maize plant, wherein said first maize plant comprises
within its genome a
marker associated with increased male fertility as described herein and said
second maize
plant optionally lacks said marker, to produce a progeny maize plant
comprising said marker;
and using a progeny maize plant comprising said marker as a pollenator in a
cross with itself
or a second maize plant that functions as a seed parent (e.g., crossing said
progeny plant
comprising said marker with itself, wherein the progeny plant functions as a
pollenator and
as a seed parent, or crossing said progeny plant comprising with a second
maize plant,
wherein the progeny plant functions as a pollenator and the second maize plant
that functions
as a seed parent), thereby improving seed production from the cross as
compared with a
suitable control cross.
In representative embodiments of the methods of the invention, the marker,
allele,
haplotype and/or genomic region comprises, consists essentially of or consists
of:
(a) one or more markers located within one or more of the
chromosomal intervals
described in Table 1 or a marker/allele/haplotype/genomic region that maps at
10 cM or less therefrom;
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(b) one or more of the desired alleles described in Table 2, Table 8 and/or
Table
10, or a marker/allele/haplotype/genomic region that maps at 10 cM or less
therefrom;
(c) a haplotype comprising two or more of the desired alleles described in
Table
2, Table 8 and/or Table 10, or a marker/allele/haplotype/genomic region that
maps at 10 cM or less therefrom;
(d) an allele or haplotype that is in linkage disequilibrium with one or
more of the
chromosomal intervals described in Table 1 or a
marker/allele/haplotype/genomic region that maps at 10 cM or less therefrom;
(e) an allele or haplotype that is in linkage disequilibrium with one or
more of the
desired alleles described in Table 2, Table 8 and/or Table 10, or a
marker/allele/haplotype/genomic region that maps at 10 cM or less therefrom;
(f) an allele or haplotype that is in linkage disequilibrium with a
haplotype
comprising two or more of the desired alleles described in Table 2, Table 8
and/or Table 10, or a marker/allele/haplotype/genomic region that maps at 10
cM or less therefrom; or
(g) any combination of (a) to (f).
In further embodiments of the methods of the invention, the
marker/allele/haplotype/genomic region is located within:
(a) chromosomal interval 1 as described in Table 1;
(b) chromosomal interval 2 as described in Table 1;
(c) one or more of chromosomal intervals 3 to 17 as described in Table 1;
(d) one or more of chromosomal interval 18 to 45 as described in Table 1;
(e) one or more of chromosomal intervals 46 to 12743 as described in Table
1;
(f) one or more of chromosomal intervals 12744 to 12749 as described in
Table 1;
(g) one or more of chromosomal intervals 12750 to 12755 as
described in Table 1;
(10 chromosomal interval 12756 as described in Table 1;
(i) one or more of chromosomal intervals 12757 to 12762 as described in
Table 1;
(j) one or more of chromosomal intervals 12763 to 12768 as described in
Table 1;
(k) one or more of chromosomal intervals 6 to 9371 as described in Table 1;
(1) chromosomal interval 3 as described in Table 1;
(m) chromosomal interval 13 as described in Table 1;
(n) chromosomal interval 25 as described in Table 1; or
(o) any combination of (a) to (n).
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In some embodiments, the marker/allele/haplotype/genomic region comprises,
consists essentially of or consists of one or more of the desired alleles:
(a) on chromosome 5 as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as describcd in Table 8;
(g) on chromosomes 3,5 and? as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8;
(j) any combination of (a) to (i); or
(k) or a marker/allele/haplotype/genornic region that maps at 10 cM or less
from
any of (a) to (j).
In other representative embodiments, the marker/allele/haplotype/genomic
region
comprises a haplotype comprising two or more of the desired alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(0 on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8;
(j) any combination of (a) to (i); or
(k) or a marker/allele/haplotype/genomic region that maps at 10 cM or less
from
any of (a) to (j).
In some embodiments, non-naturally occurring maize plants and plant parts
comprising one or more markers, alleles and/or genomic regions associated with
increased
male fertility (e.g., maize plants and plant identified, selected and/or
produced according to
methods of the invention) are provided.
In some embodiments, progeny and plant parts derived from maize plants and
plant
parts comprising one or more markers, alleles and/or genomic regions
associated with
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increased male fertility (e.g., maize plants and plant identified, selected
and/or produced
according to methods of the invention) are provided.
In some embodiments, isolated and/or purified markers associated with
increased
male fertility are provided. Such markers may comprise, consist essentially of
or consist of
one or more of the nucleotide sequences set forth in SEQ ID NOs: 1-350, the
reverse
complement thereof, or an informative or functional fragment thereof.
In some embodiments, isolated and/or purified quantitative trait loci (QTLs)
associated with increased male fertility are provided. Such QTLs may comprise,
consist
essentially of or consist of one or more of the chromosomal segments described
in Table 1.
In some embodiments, amplification products comprising one or more markers,
alleles and/or genomic regions associated with increased male fertility are
provided. Such
amplification products may comprise, consist essentially of or consist of one
or more of the
nucleotide sequences set forth in SEQ ID NOs: 1 to 350, the reverse complement
thereof, or
an informative or functional fragment thereof.
In some embodiments, probes (e.g., as described in Table 9) for detecting one
or more
markers, alleles and/or genomic regions associated with increased male
fertility are provided.
Such probes may comprise, consist essentially of, or consist of one or more of
the nucleotide
sequences set forth in SEQ ID NOs: 526 to 613, the reverse complement thereof,
or an
informative or functional fragment thereof.
The foregoing and other objects and aspects of the present invention are
explained in
detail in the drawings and specification set forth below.
BRIEF DESCRIPTION OF THE TABLES
Table 1 describes segments of maize chromosomes 1, 3,4, 5, 6, 7, 8, 9 and 10.
Table 2 describes alleles of interest located on maize chromosome 5.
Table 3 describes proteins of interest encoded by maize chromosome 5, as well
as the
segments of chromosome 5 that encode those proteins.
Table 4 describes Vip3 proteins and the nucleic acid sequences encoding those
proteins.
Table 5 shows that Vip3-induced reductions in male fertility vary across
genetic
backgrounds.
Table 6 shows the LOD (logorithm of the odds) scores of QTLs (quantitative
trait
locus) identified using F2 plants from bi-parental crosses of NP2222
(described in U.S.
Patent No. 6,710,233) and NP2276 (described in U.S. Patent No. 6,706,955) and
bi-parental
9
crosses of 1D3461 (described in International Patent Application No.
W02009142752) and
NP2276.
Table 7 shows the Fertility Index used to score F2 plants from bi-parental
crosses of
NP2222 and NP2276 and bi-parental crosses of ID3461 and NP2276.
Table 8 describes QTLs associated with increased anther quantity and/or
improved
anther quality in maize plants expressing a Vip3 protein.
Table 9 describes exemplary nucleic acid probes and primers useful to identify
the
favorable alleles in the QII.s described in Table I.
Table 10 describes SNPs present in inbred maize line NP2222 versus line NP2276
across the male fertility-associated QTL intervals in Table 8. Where the
alleles differ
between the two lines, the NP2222 allele corresponds to the desired
(favorable) allele.
Table 11 provides public lines predicted to contain favorable alleles.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a chart comparing anther quantity of Vip3-expressing NP2276 inbred
lines
grown under varying thermal and moisture conditions.
Fig. 2 shows that thermal stress exacerbates Vip3-induced reductions in male
fertility.
DETAILED DESCRIPTION
The present invention provides maize plants having increased fertility, as
well as
compositions and methods for identifying, selecting and producing maize plants
and plant
parts having one or more characteristics associated with increased fertility.
Although the following terms are believed lobe well understood by one of
ordinary
skill in the art, the following definitions are set forth to facilitate
understanding of the
presently disclosed subject matter.
All technical and scientific terms used herein, unless otherwise defined
below, are
intended to have the same meaning as commonly understood by one of ordinary
skill in the
art References to techniques employed herein are intended to refer to the
techniques as
commonly understood in the art, including variations on those techniques or
substitutions of
equivalent techniques that would be apparent to one of skill in the art.
Unless otherwise specified, genetic loci are described herein with respect to
their
positions in the Maize B73 Ref Gen_v2 reference genome (available at
www.maizegdb.org).
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Unless otherwise specified, nucleotides are described herein using the
following standard
abbreviations: adenine (A), cytosine (C), thymine (T), guanine (G), uracil
(U), adenine or
guanine (R), cytosine or thymine/uracil (Y), adenine or cytosine (M), guanine
or
thymine/uracil (K), guanine or cytosine (S), adenine or thymine/uracil (W),
guanine or
cytosine or thymine/uracil (B), adenine or guanine or thymine/uracil (D),
adenine or cytosine
or thymine/uracil (H), adenine or guanine or cytosine (V) and adenine or
guanine or cytosine
or thymine/uracil (N).
Unless otherwise specified, amino acids are described herein using the
following
standard abbreviations: alanine (Ala; A), arginine (Arg; R), asparagine (Asn;
N), aspartic acid
(Asp; D), cysteine (Cys; C), glutamine (Gin; Q), glutamic acid (Glu; E),
glycine ((lily; G),
histidine (His; H), isoleucine (Ile; 1), leucine (Lea; L), lysine (Lys; K),
methionine (Met; M),
phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; 1),
tryptophan (Tip;
W), tyrosine (Tyr; Y), and valine (Val; V).
As used herein, the terms "a" or "an" or "the" may refer to one or more than
one. For
example, "a" marker can mean one marker or a plurality of markers.
As used herein, the term "and/or" refers to and encompasses any and all
possible
combinations of one or more of the associated listed items, as well as the
lack of
combinations when interpreted in the alternative ("or").
As used herein, the term "about," when used in reference to a measurable value
such
as an amount of mass, dose, time, temperature, and the like, is meant to
encompass variations
of 20%, 10%, 5%, 1%, 0.5%, or even 0.1% of the specified amount.
As used herein, the term "allele" refers to one of two or more different
nucleotides or
nucleotide sequences (or the absence thereof) that occur at a specific locus
or set of
contiguous loci, In some embodiments, the term "allele" may be used
interchangeably with
the term "marker."
As used herein, the terms "allele of interest," "desired allele" and"favorable
allele" are
used interchangeably to refer to an allele that is linked to a desired trait.
An "allele of
interest" may be associated with either an increase or decrease of or in a
given trait,
depending on the nature of the desired phenotype, and may be associated with a
change in
morphology, color, etc. In some embodiments of the present invention, the
"allele of
interest" is associated with increased male fertility and may therefore be
used as a marker to
identify, select and/or produce fertile maize plants; to predict whether
and/or to what extent a
maize plant will be fertile; to reduce the costs associated with breeding
and/or seed
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production programs; and/or to increase the efficiency of breeding and/or seed
production
programs.
As used herein, the terms "backcross' and "ba.ckcrossing" refer to the process
whereby a progeny plant is crossed back to one of its parents for one or more
generations
(e.g., 2 or more, 3 or more, 4 or snore, 5 or more, 6 or more, or 7 or more
times, etc.). In a
backcrossing scheme, the "donor" parent refers to the parental plant with the
desired gene or
locus to be introgressed. The "recipient" parent (used one or more times) or
"recurrent"
parent (used two or more times) refers to the parental plant into which the
gene or locus is
being introgressed. For example, see Ragot et al. Marker-assisted
Backcrossing: A Practical
Example, in TECHNIQUES ET UTIIISATIONS DES MAR.QUEURS MOLECULAIRES Las
COLLOQUES,
Vol. 72, pp. 45-56 (1995); and Openshaw et al., Marker-assisted Selection in
Backcross
Breeding, in PROCEEDINGS OF ME SYMPOSIUM "ANALYSIS OF MOLECULAR MARKER DATA,"
pp. 41-43 (1994). The initial cross gives rise to the Fl generation. The term
''BC1" refers to
the second use of the recurrent parent, "BC2" refers to the third use of the
recurrent parent,
and so on. In embodiments, at least one or more generations of progeny are
identified and/or
selected for the presence of the desired gene or locus (e.g., in a nucleic
acid sample from the
progeny plant or plant part). In embodiments, two or more generations (or even
all
generations) of progeny are identified and/or selected for the presence of the
desired gene or
locus.
As used herein, the term "closely linked loci" refers to genetic loci that
display an
inter-locus recombination frequency of about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%,
2%, 1%,
0.75%, 0.5%, 0.25% or less. Since one cM equals the distance between two loci
that show a
1% recombination frequency, closely linked loci on the same chromosome will
reside at
about 10, 9, 8, 7, 6, 5, 4, 3,2, 1, 0.75, 0.5 or 0.25 cM or less from another.
Such loci may be
said to be "proximal to" one another.
As used herein, the terms "centimorgan" and "cM" refer to a unit of measure of
recombination frequency. One cM is equal to a 1% chance that a marker at one
genetic locus
will be separated from a marker at a second locus due to crossing over in a
single generation.
As used herein, the term "coding sequence" refers to a nucleic acid sequence
that is
transcribed into RNA such as mRNA, rRNA, tRNA, snRNA, shRNA, sense RNA or
antisense RNA. The RNA may be translated to produce a polypeptide.
As used herein, the term "completely fertile" refers to a plant that is at
least as fertile
as a control plant (e.g., one or both of its parents, a near isogenic plant
that lacks one or more
markers/alleles associated with increased fertility, a near isogenic plant
that lacks a v1p3
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coding sequence, etc.). In some embodiments, "completely fertile" plants
release at least as
many pollen grains per tassel per day in the three-day period immediately
following anther
extrusion as the control plant. In some embodiments, "completely fertile"
plants release more
pollen grains per tassel per day in the three-day period immediately following
anther
extrusion than the control plant.
As used herein, the terms "cross" or "crossed" refer to the fusion of gametes
via
pollination to produce progeny (e.g., cells, seeds or plants). The term
encompasses both
sexual crosses (the pollination of one plant by another) and selling (self-
pollination, e.g.,
when the pollen and ovule are from the same plant). The term "crossing" refers
to the act of
fusing gametes via pollination to produce progeny.
As used herein, the terms "cultivar" and "variety" refer to a group of similar
plants
that by structural or genetic features and/or performance can be distinguished
from other
varieties within the same species.
As used herein, the term "cultivated" refers to a plant that is no longer in
the natural
state, but has been developed and domesticated by human care and for
agricultural use and/or
human consumption. "Cultivated" plants, as used herein, excludes native plants
that
comprise the subject trait of this invention as a natural trait and/or as part
of its natural
genetics.
As used herein, the terms "decrease," "decreases," "decreasing" and similar
terms
refer to a reduction of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,
45%, 50%,
55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more. In
some
embodiments, the reduction results in no or essentially no activity an
insignificant or
undetectable amount of activity).
As used herein, the terms "elite" and "elite line" refer to any line that has
resulted
from breeding and selection for desirable agronomic performance. An elite line
may be
substantially homozygous. Numerous elite lines are available and known to
those of skill in
the art.
As used herein, the term "elite germplasm" refers to any germplasm that is
derived
from or is capable of giving rise to an elite plant.
As used herein, the term "event" refers to a particular transforrnant In a
typical
transgenic breeding program, a transformation construct responsible for a
trait is introduced
into the genome via a transformation method. Numerous independent
transformants (events)
are usually generated for each construct. These events are evaluated to select
those with
superior performance.
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As used herein, with respect to nucleic acids, the term "exogenous" refers to
a nucleic
acid that is not in the natural genetic background of the cell/organism in
which it resides. In
some embodiments, the exogenous nucleic acid comprises one or more nucleic
acid
sequences that are not found in the natural genetic background of the
cell/organism. In some
embodiments, the exogenous nucleic acid comprises one or more additional
copies of a
nucleic acid that is endogenous to the cell/organism.
As used herein, the term "expression cassette" refers to a nucleotide capable
of
directing expression of a particular nucleic acid sequence in a host cell
(e.g., a maize cell). In
some embodiments, the expression cassette comprises, consists essentially of
or consists of
one or more promoter sequences (e.g, one or more constitutive/inducible
promoter
sequences, one or more tissue- and/or organ-specific promoter sequences and/or
one or more
developmental stage-specific promoter sequences) operably linked to a nucleic
acid of
interest, which is operably linked to a termination sequence. Expression
cassettes often
comprise sequences required for proper translation of the nucleic acid
sequence of interest in
the host cell. The expression cassette may be chimeric in that at least one of
its components
is heterologous with respect to at least one of its other components. The
expression cassette
may be one that is naturally occurring but that has been obtained in a
recombinant form
useful for heterologous expression. Typically, however, the expression
cassette is
heterologous with respect to the host (i.e., the particular nucleic acid
sequence of the
expression cassette does not occur naturally in the host cell and must have
been introduced
into the host cell or an ancestor of the host cell by a transformation event).
As used herein with respect to nucleic acids, the term "fragment" refers to a
nucleic
acid that is reduced in length relative to a reference nucleic acid and that
comprises, consists
essentially of and/or consists of a nucleotide sequence of contiguous
nucleotides identical or
almost identical (e.g, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%
identical) to a
corresponding portion of the reference nucleic acid. Such a nucleic acid
fragment may be,
where appropriate, included in a larger polynucleotide of which it is a
constituent. In some
embodiments, the nucleic acid fragment comprises, consists essentially of or
consists of at
least about 5,6, 7, 8,9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50,
55, 60, 65, 70, 75,
80, 85, 90, 95, 100, 125, 150, 175, 200, 225, 250, 300, 350, 400, 450, 500, or
more
consecutive nucleotides. In some embodiments, the nucleic acid fragment
comprises,
consists essentially of or consists of less than about 5, 6, 7, 8, 9, 10, 11,
12, 13, 14, 15,20, 25,
30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175,
200, 225, 250, 300,
350, 400, 450 or 500 consecutive nucleotides.
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As used herein with respect to polypeptides, the teens "fragment" refers to a
polypeptide that is reduced in length relative to a reference polypeptide and
that comprises,
consists essentially of and/or consists of an amino acid sequence of
contiguous amino acids
identical or almost identical (e.g., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,
98%, 99%
identical) to a corresponding portion of the reference polypeptide. Such a
polypeptide
fragment may be, where appropriate, included in a larger polypeptide of which
it is a
constituent. In some embodiments, the polypeptide fragment comprises, consists
essentially
of or consists of at least about 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14,
15, 20, 25, 30, 35, 40,
45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 125, 150, 175, 200, 225, 250,
300, 350, 400,
450, 500, or more consecutive amino acids. In some embodiments, the
polypeptide fragment
comprises, consists essentially of or consists of less than about 2, 3, 4, 5,
6,7, 8, 9, 10, 11, 12,
13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80,85, 90, 95,
100, 125, 150, 175,
200, 225, 250, 300, 350, 400, 450 or 500 consecutive amino acids.
As used herein with respect to nucleic acids, the term "functional fragment"
refers to
nucleic acid that encodes a functional fragment of a polypeptide.
As used herein with respect to polypeptides, the term "functional fragment"
refers to
polypeptide fragment that retains at least about 20%, 25%, 30%, 35%, 40%, 45%,
50%, 55%,
60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more of at least
one
biological activity of the full-length polypeptide (e.g, the ability to
convert all-trans-I3-
carotene into 9-cis-13-carotene). In some embodiments, the functional fragment
actually has a
higher level of at least one biological activity of the full-length
polypeptide.
As used herein, the Willis "fertile" and "functionally fertile" are used
interchangeably
and refer to a plant that is fertile enough for use in a breeding and/or seed
production
program. In some embodiments, "functionally fertile" plants are plants that
release at least
about 100,000; 150,000; 200,000; 250,000, 300,000, 350,000, 400,000 or 450,000
pollen
grains per tassel per day in the three-day period immediately following anther
extrusion.
As used herein, the term "gene product" refers to a material resulting from
expression
of a nucleic acid. In some embodiments, the gene product is an RNA molecule
(e.g, an
mRNA molecule or an antisense RNA molecule). In some embodiments, the gene
product is
a polypeptide.
As used herein, the term "genetic map" refers to a description of genetic
linkage
relationships among loci on one or more chromosomes within a given species,
generally
depicted in a diagrammatic or tabular form. For each genetic map, distances
between loci are
measured by the recombination frequencies between them. Recombinations between
loci can
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be detected using a variety of markers. A genetic map is a product of the
mapping
population, types of markers used, and the polymorphic potential of each
marker between
different populations. The order and genetic distances between loci can differ
from one
genetic map to another.
As used herein, the term "genetic marker" refers to one or more nucleotides
associated
with a phenotype, trait or trait form of interest. In some embodiments, a
marker may be
associated with an allele or alleles of interest and may be indicative of the
presence or
absence of the allele or alleles of interest in a cell or organism. In some
embodiments, the
marker may comprise, consist essentially of, or consist of an allele or
alleles of interest. A
marker may be, but is not limited to, an allele, a haplotype, a restriction
fragment length
polymorphism (RFLP), a simple sequence repeat (SSR), random amplified
polymorphic
DNA (RAPD), cleaved amplified polymorphic sequences (CAPS) (Rafa1ski and
Tingey,
Trends in Genetics 9:275 (1993)), an amplified fragment length polymorphism
(AFLP) (Vos
et al., Nucleic Acids Res. 23:4407 (1995)), a single nucleotide polymorphism
(SNP)
(Brookes, Gene 234:177 (1993)), a sequence-characterized amplified region
(SCAR) (Paran
and Michelmore, Theor. App!. Genet. 85:985 (1993)), a sequence-tagged site
(STS) (Onozaki
et al., Euphytica 138:255 (2004)), a single-stranded conformation polymorphism
(SSCP)
(Grits et al., Proc. Natl. Acad. Sci. USA 86:2766 (1989)), an inter-simple
sequence repeat
USSR) (Blair et al., Theor. App!. Genet. 98:780(1999)), an inter-
retrotransposon amplified
polymorphism (IRAP), a retrotransposon-microsatellite amplified polymorphism
(REMAP)
(Kalendar et al., Theor. App!. Genet. 98:704 (1999)) or an RNA cleavage
product (such as a
Lynx tag). A marker may be present in genomic or expressed nucleic acids
(e.g., ESTs).
Some of the markers described herein are also referred to as hybridization
markers when
located on an indel region. This is because the insertion region is, by
definition, a
polymorphism vis-a-vis a plant without the insertion. Thus, the marker need
only indicate
whether the indel region is present or absent Any suitable marker detection
technology may
be used to identify such a hybridization marker, e.g., SNP technology is used
in the examples
provided herein. A large number of maize genetic markers are known in the art,
and are
published or available from various sources, such as the Maize GDB intemet
resource and the
Arizona Genomics Institute intemet resource run by the University of Arizona.
As will be understood by those skilled in the art, "genetic markers" may
comprise
"dominant" and/or "codominant" markers. "Codominant markers" reveal the
presence of two
or more alleles (two per diploid individual). "Dominant markers" reveal the
presence of only
a single allele. The presence of the dominant marker phenotype (e.g., a band
of DNA) is an
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indication that one allele is present in either the homozygous or heterozygous
condition. In
the case of populations where individuals are predominantly homozygous and
loci are
predominantly dimorphic, dominant and codominant markers can be equally
valuable. As
populations become more heterozygous and multiallelic, codominant markers
often become
more informative of the genotype than dominant markers.
As used herein, the term "genotype" refers to the genetic constitution of an
individual
(or group of individuals) at one or more genetic loci, as contrasted with the
observable and/or
detectable and/or manifested trait (the phenotype). Genotype is defined by the
allele(s) of
one or more known loci that the individual has inherited from its parents. The
term genotype
can be used to refer to an individual's genetic constitution at a single
locus, at multiple loci, or
more generally, the term genotype can be used to refer to an individual's
genetic make-up for
all the genes in its genome. Genotypes can be indirectly characterized, e.g.,
using markers
and/or directly characterized by nucleic acid sequencing.
As used herein, the term "germplasm" refers to genetic material of or from an
individual plant, a group of plants (e.g., a plant line, variety or family),
or a clone derived
from a plant line, variety, species, or culture. The genetic material can be
part of a cell, tissue
or organism, or can be isolated from a cell, tissue or organism.
As used herein, the term "haplotype" refers to a combination of alleles (two
or more)
at a plurality of genetic loci. Typically, the genetic loci that define a
haplotype are physically
and genetically linked (i.e., the alleles that make up a haplotype are
generally located on the
same chromosome segment). Thus, in some embodiments, the term ''haplotype"
refers to a
plurality of alleles within a single chromosomal segment or to a plurality of
alleles within two
or more chromosomal segments residing on the same chromosome.
As used herein, the terms "haplotype of interest" and "desired haplotype "are
sed
interchangeably to refer to a haplotype that is linked to a desired trait. A
"haplotype of
interest" may be associated with either an increase or decrease of or in a
given trait,
depending on the nature of the trait, and may be associated with a change in
morphology,
color, etc. In some embodiments of the present invention, the "haplotype of
interest" is
associated with increased male fertility and may therefore be used as a marker
to identify,
select and/or produce fertile maize plants; to predict whether and/or to what
extent a maize
plant will be fertile; to reduce the costs associated with breeding and/or
seed production
programs; and/or to increase the efficiency of breeding and/or seed production
programs.
As used herein, the term "hemizygous" refers to a genetic status in a diploid
cell in
which there is only one copy of a gene instead of the typical two copies (i.e.
, the gene has no
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countetpart on a homologous chromosome). For example, in mammals, the genes on
the X
chromosome are hemizygous in males. As another illustration, a heterologous
transgene can
be present in a hemizygous state.
As used herein, the term "heterologous" refers to a nucleofide/polypeptide
that
originates from a foreign species, or, if from the same species, is
substantially modified from
its native form in composition and/or genomic locus by deliberate human
intervention.
As used herein, the term "heterotic group" refers to a set of genotypes that
display
similar heterotic response when crossed with genetically distinct groups of
genotypes (i.e.,
when crossed with genotypes from a different heterotic grou4p). Hallatt-r et
al., Corn
breeding, in CORN AND CORN IMPROVEMENT p. 463-564 (1998). Inbred lines are
classified
into heterotic groups, and are further subdivided into families within a
heterotic group, based
on several criteria such as pedigree, molecular marker-based associations, and
performance in
hybrid combinations. Smith et al., Theor. AppL Gen. 80:833 (1990). The "Stiff
Stalk"
heterotic group represents a major heterotic group in the northern U.S. and
Canadian corn
growing regions; it is sometimes referred to as the "Iowa Stiff Stalk
Synthetic" or "BSSS"
heterotic group. The "non-Stiff Stalk" heterotic group represents a major
heterotic group in
the northern U.S. and Canadian corn growing regions; it is sometimes referred
to as the
"Lancaster" or "Lancaster Sure Crop" heterotic group.
As used herein, the term "heterozygous" refers to a genetic status wherein
different
alleles reside at corresponding loci on homologous chromosomes.
As used herein, the term "homozygous" refers to a genetic status wherein
identical
alleles reside at corresponding loci on homologous chromosomes.
As used herein, the term "hybrid" refers to a plant or plant part produced
when at least
two genetically dissimilar parents are crossed. Without limitation, examples
of mating
schemes include single crosses, modified single crosses, double modified
single crosses,
three-way crosses, modified three-way crosses, and double crosses, wherein at
least one
parent in a modified cross is the progeny of a cross between sister lines.
As used herein, the team "inbred" refers to a substantially homozygous plant
or
variety. The term may refer to a plant or variety that is substantially
homozygous throughout
the entire genome or that is substantially homozygous with respect to a
portion of the genome
that is of particular interest. Without limitation, examples of breeding
methods to derive
inbreds include pedigree breeding, recurrent selection, single-seed descent,
backcrossing, and
doubled haploids.
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As used herein, the terms "increase," "increases," "increasing" and similar
terms refer
to an augmentation of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,
45%, 50%,
55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, 200%,
300%
or more.
As used herein, the term "increased fertility" refers to an improvement in one
or more
fertility traits as compared to one or more controls (e.g., a native
plant/germplasm of the same
species, one or both parents, a near isogenic plant that lacks one or more
markers/alleles
associated with increased fertility, a near isogenic plant that lacks a vip3
coding sequence,
etc.). Exemplary fertility traits include, but are not limited to, pollen
count, pollen
morphology, pollen production per anther, anther count, anther morphology,
anthers per
tassel, tassel count, tassel morphology, tassels per plant, silk count, silk
morphology, silk
production per plant, kernel count, kernel morphology, kernel production per
ear, prevalence
of kernel abortion, kernel production per plant and kernel viability. Thus, a
plant that
exhibits increased pollen production, increased pollen production per anther,
improved pollen
morphology, increased anther production, increased anther production per
tassel, improved
anther morphology, increased tassel production, improved tassel morphology,
increased silk
production, improved silk morphology, increased silk production per plant,
increased kernel
count, improved kernel morphology, increased kernel production per ear,
decreased
prevalence of kernel abortion, increased kernel production per plant,
increased kernel
viability, increased fertility under stress conditions (e.g., drought
conditions), increased
fertility under elevated daytime temperatures and/or increased fertility under
elevated
nighttime temperatures as compared to a control plant (e.g., a native
plant/germplasm of the
same species, one or both parents, a near isogenic plant that lacks one or
more markers/alleles
associated with increased fertility, a near isogenic plant that lacks a vip3
coding sequence,
etc.) displays increased fertility. When used in reference to a plant part
(e.g, a germplasm),
the term "increased fertility" refers to an improvement in one or more
fertility traits in a plant
that arises from that plant part
As used herein, the term "increased female fertility" refers to an improvement
in one
or more female fertility traits as compared to one or more controls (e.g., a
native
plant/germplasin of the same species, one or both parents, a near isogenic
plant that lacks one
or more markers/alleles associated with increased fertility, a near isogenic
plant that lacks a
vip3 coding sequence, etc.). Exemplary female fertility traits include, but
are not limited to,
silk count, silk morphology, silk production per plant, kernel count, kernel
morphology,
kernel production per ear, prevalence of kernel abortion, kernel production
per plant and
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kernel viability. Thus, a plant that exhibits increased silk production,
improved silk
morphology, increased silk production per plant, increased kernel count,
improved kernel
morphology, increased kernel production per ear, decreased prevalence of
kernel abortion,
increased kernel production per plant, increased kernel viability, increased
female fertility
under stress conditions (e.g., drought conditions), increased female fertility
under elevated
daytime temperatures and/or increased female fertility under elevated
nighttime temperatures
as compared to a control plant (e.g., a native plant/germplasm of the same
species, one or
both parents, a near isogenic plant that lacks one or more markers/alleles
associated with
. increased fertility, a near isogenic plant that lacks a vip3 coding
sequence, etc.) displays
increased female fertility. When used in reference to a plant part (e.g., a
germplasm), the
term "increased female fertility" refers to an improvement in one or more
female fertility
traits in a plant that arises from that plant part.
As used herein, the term "increased male fertility" refers to an improvement
in one or
more male fertility traits as compared to one or more controls (e.g., a native
plant/germplasm
of the same species; one or both parents, a near isogenic plant that lacks one
or more
markers/alleles associated with increased fertility, a near isogenic plant
that lacks a v1p3
coding sequence, etc.). Exemplary male fertility traits include, but are not
limited to, pollen
count, pollen morphology, pollen production per anther, anther count, anther
morphology,
anthers per tassel, tassel count, tassel morphology and tassels per plant
Thus, a plant that
exhibits increased pollen production, increased pollen production per anther,
improved pollen
morphology, increased anther production, increased anther production per
tassel, improved
anther morphology, increased tassel production, improved tassel morphology,
increased male
fertility under stress conditions (e.g., drought conditions), increased male
fertility under
elevated daytime temperatures and/or increased male fertility under elevated
nighttime
temperatures as compared to a control plant (e.g., a native plant/germplasm of
the same
species, one or both parents, a near isogenic plant that lacks one or more
markers/alleles
associated with increased fertility, a near isogenic plant that lacks a v1p3
coding sequence,
etc.). displays increased male fertility. When used in reference to a plant
part (e.g., a
germplasm), the term "increased male fertility" refers to an improvement in
one or more male
fertility traits in a plant that arises from that plant part.
As used herein, the term "indel" refers to an insertion or deletion in a pair
of
nucleotide sequences, wherein a first sequence may be referred to as having an
insertion
relative to a second sequence or the second sequence may be referred to as
having a deletion
relative to the first sequence.
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As used herein, the term "infertile" refers to a plant that is insufficiently
fertile for use
in a breeding program. In some embodiments, "infertile" plants are plants that
release fewer
than 25,000; 50,000; 75,000 or 100,000 pollen grains per tassel per day in the
three-day
period immediately following anther extrusion. "Infertile" plants may produce
andior release
viable pollen grains. Indeed, in some embodiments, "infertile" plants produce
and release
viable pollen grains, but do so a rate that is insufficient for effective use
in a breeding and/or
seed production program.
As used herein, the term "informative fragment" refers to a nucleotide
sequence
comprising a fragment of a larger nucleotide sequence, wherein the fragment
allows for the
identification of one or more alleles within the larger nucleotide sequence.
For example, an
informative fragment of the nucleotide sequence of SEQ ID NO: 1 comprises a
fragment of
the nucleotide sequence of SEQ ID NO: 1 and allows for the identification of
one or more
alleles of interest located within the portion of the nucleotide sequence
corresponding to that
fragment of SEQ ID NO: I.
As used herein, the terms "introgression," "introgressing" and "introgressed"
refer to
both the natural and artificial transmission of a desired allele or
combination of desired alleles
of a genetic locus or genetic loci from one genetic background to another. For
example, a
desired allele at a specified locus can be transmitted to at least one progeny
via a sexual cross
between two parents of the same species, where at least one of the parents has
the desired
allele in its genome. Alternatively, for example, transmission of an allele
can occur by
recombination between two donor genomes, e.g., in a fused protoplast, where at
least one of
the donor protoplasts has the desired allele in its genome. The desired allele
may be a
selected allele of a marker, a QTL, a transgene, or the like. Offspring
comprising the desired
allele can be repeatedly backcrossed to a line having a desired genetic
background and
selected for the desired allele, with the result being that the desired allele
becomes fixed in
the desired genetic background. For example, a marker associated with
increased fertility
may be introgressed from a donor into a recurrent parent that is not
functionally fertile. The
resulting offspring could then be repeatedly backcrossed and selected until
the progeny
possess the enhanced fertility allele in the recurrent parent background.
As used herein with respect to nucleotides and polypeptides, the term
"isolated" refers
to a nucleotide or polypeptide that is substantially free of cellular
material, viral material,
culture medium (when produced by recombinant DNA techniques), or chemical
precursors or
other chemicals (when chemically synthesized). An "isolated fragment" is a
fragment of a
nucleotide or polypeptide that is not naturally occurring as a fragment and
would not be
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found in the natural state. "Isolated" does not mean that the preparation is
technically pure
(homogeneous), but rather that it is sufficiently pure to provide the
nucleotide or polypeptide
in a form in which it can be used for the intended purpose. In certain
embodiments, the
composition comprising the nucleotide or polypeptide is at least about 50%,
55%, 60%, 65%,
70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more pure.
As used herein with respect to cells, the term "isolated" refers to a cell
that is
separated from other components with which it is normally associated in its
natural state. For
example, an isolated plant cell may be a plant cell in culture medium and/or a
plant cell in a
suitable carrier. "Isolated" does not mean that the preparation is technically
pure
(homogeneous), but rather that it is sufficiently pure to provide the cell in
a form in which it
can be used for the intended puipose. In certain embodiments, the composition
comprising
the cell is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, or 99% or more pure.
As used herein, the term "linkage" refers to the degree to which a marker is
associated
with a given allele and/or phenotypic trait (e.g., increased male fertility).
The more closely a
marker is linked to an allele/phenotype, the better an indicator that marker
becomes. The
degree of linkage between a marker and a phenotypic trait may be measured and
expressed as
the statistical probability of cosegregation of the marker and phenotypic
trait. The linkage
relationship between a marker and an allele/phenotype may be given as a
"probability" or
"adjusted probability." Linkage can be expressed as a desired limit or range.
For example, in
some embodiments, two genetic markers are deemed to be linked if they are
separated by less
than about 50, 40, 30, 25,20, 15, 10, 5, 4, 3, 2, or 1 GM. In representative
embodiments, two
genetic markers are linked if they are separated by 10cM or less.
As used herein, the term "linkage disequilibrium" refers to a non-random
segregation
of genetic loci or traits (or both). Linkage disequilibrium implies that the
relevant loci are
within sufficient physical proximity along a length of a chromosome so that
they segregate
together with greater than random (i.e., non-random) frequency.
Markers/alleles that show
linkage disequilibrium are considered linked. Linked markers/alleles co-
segregate more than
50% of the time. In other words, markers/alleles that co-segregate have a
recombination
frequency of less than 50%. Linkage disequilibrium is most commonly assessed
using the
measure ?, which is calculated using the formula described by Hill and
Robertson, Thear.
App!. Genet. 38:226(1968). When r2=1, complete linkage disequilibrium exists
between the
markers/alleles, meaning that the markers have not been separated by
recombination and
have the same allele frequency. Values for r2 above 1/3 generally indicate
sufficiently strong
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linkage disequilibrium to be useful for mapping. Ardlie et al., Nature Reviews
Genetics 3:299
(2002). Hence, in some embodiments, markers/alleles are said to be in linkage
disequilibrium when? values between pairwise marker loci are greater than or
equal to about
0.33, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1Ø
As used herein, the term "linkage equilibrium" describes a situation where
markers/alleles independently segregate (i.e., sort among progeny randomly).
Markers that
show linkage equilibrium are considered unlinked (whether or not they lie on
the same
chromosome).
As used herein, the term "linkage group" refers to a group of genes associated
together by linkage relationships.
As used herein, the term "locus" refers to a position on a chromosome. Loci
may
encompass one or more nucleotides.
As used here, the terms "logarithm of odds" and "LOD score" refer to the
likelihood
that two genetic loci are linked. LOD scores are most commonly assessed using
the measure
Z, which is equal to the logarithm of the ratio of the likelihood that the
genetic loci are linked
and 0.5 times the likelihood that the two genetic loci are independently
sorted. Positive LOD
scores are indicative of linkage, whereas negative LOD scores are indicative
of independent
assortment. LOD scores of 2.5 and higher generally sufficiently strong linkage
to be useful
for mapping. Hence, in some embodiments, markers/alleles are said to be linked
when the
LOD score is greater than or equal to about 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6,
6.5, 7, 7.5, 8, 8.5, 9,
9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more.
As used herein, the term "maize" refers to Zea mays L. subsp. mays. In some
embodiments, the maize plant or plant part is from the group Zea mays L.
subsp. mays
Identata, sometimes referred to as dent corn. In some embodiments, the maize
plant or plant
part is from the group Zea mays L. subsp. mays Indurata, sometimes referred to
as flint corn.
In some embodiments, the maize plant or plant part is from the group Zea mays
L. subsp.
mays Saccharata, sometimes referred to as sweet corn. In some embodiments, the
maize
plant or plant part is from the group Zea mays L. subsp. mays Amylacea,
sometimes referred
to as flour corn. In some embodiments, the maize plant or plant part is from
the group Zea
mays L. subsp. mays Everts, sometimes referred to as pop corn. Maize plants
that can be
identified selected and/or produced with methods and compositions of the
present invention
include hybrids, inbreds, partial inbreds, members of defined populations and
members of
undefined populations.
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As used herein, the terms "male fertile" and "male fertility" refer to the
ability of a
plant to produced and release viable, functional pollen grains.
As used herein, the terms "male sterile" and "male sterility" refer to the
inability of a
plant to produce and/or release viable, functional pollen grains. Male
sterility generally
occurs as a result of failure of formation or development of functional
stamens, microspores
or gametes. Typically there are three types of male sterility: 1) "pollen
sterility" in which
male sterile individuals differ from normal only in the absence or extreme
scarcity of
functional pollen grains; 2) "structural or staminal male sterility" in which
male flowers or
stamen are malformed and non-functional or completely absent and 3)
"functional male
sterility" in which perfectly good and viable pollen is trapped in indehiscent
anther and thus
prevented from functioning.
As used herein, the term "marker" refers to a detectable characteristic that
can be used
to discriminate between organisms. Examples of such characteristics may
include genetic
composition (e.g., genetic marker), gene expression levels, protein
composition, protein
levels, oil composition, oil levels, carbohydrate composition, carbohydrate
levels, fatty acid
composition, fatty acid levels, amino acid composition, amino acid levels,
biopolymers,
pharmaceutical, starch composition, starch levels, fermentable starch,
fermentation yield,
fermentation efficiency, energy yield, secondary compounds, metabolites,
morphological
characteristics, and agronomic characteristics.
A marker is "associated with" a trait when it is linked to it and when the
presence of
the marker is an indicator of whether and/or to what extent the desired trait
or trait form will
occur in a plant/plant part comprising the marker. Similarly, a marker is
"associated with" an
allele when it is linked to it and when the presence of the marker is an
indicator of whether
the allele is present in a plant/plant part comprising the marker. For
example, "a marker
associated with increased male fertility" refers to a marker whose presence or
absence can be
used to predict whether and/or to what extent a plant/plant part will display
increased male
fertility.
Markers corresponding to genetic polymorphisms between members of a population
can be detected by methods well-established in the art. These include, e.g.,
nucleic acid
sequencing, hybridization methods, amplification methods (e.g., PCR-based
sequence
specific amplification methods), detection of restriction fragment length
polymorphisms
(RFLP), detection of isozyme markers, detection of polynucleotide
polymorphisms by allele
specific hybridization (ASH), detection of amplified variable sequences of the
plant genome,
detection of self-sustained sequence replication, detection of simple sequence
repeats (SSRs),
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detection of single nucleotide polymorphisms (SNPs), and/or detection of
amplified fragment
length polymorphisms (AFLPs). Well established methods are also known for the
detection
of expressed sequence tags (ESTs) and SSR markers derived from EST sequences
and
randomly amplified polymorphic DNA (RAPD).
As used herein, the terms "marker allele" and "allele of a marker locus" refer
to one of
a plurality of polymorphic nucleotides or nucleotide sequences found at a
marker locus in a
population that is polymorphic for the marker locus.
As used herein, the term "marker locus" refers to a specific chromosome
location in
the genome of an organism where a specific marker can be found. A marker locus
can be
used to track the presence of a second linked locus, e.g., a linked locus that
encodes or
contributes to expression of a phenotypic trait. For example, a marker locus
can be used to
monitor segregation of alleles at a locus, such as a QTL or single gene, that
are genetically or
physically linked to the marker locus.
As used herein, the terms "marker probe" and "probe" refer to a molecule that
can be
used to detect the presence of one or more particular alleles, haplotypes
and/or molecules of
interest. In some embodiments, a "marker probe" is a nucleic acid sequence
that is
complementary to all of or a portion of an allele of interest. Marker probes
(as described in
Table 9) comprising 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25,
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,
45, 46, 47, 48, 49, 50
or more contiguous nucleotides may be used for nucleic acid hybridization. In
some
embodiments, the marker probe comprises at least about 7, 10, 15, 20,25, 30,
35, 40,45, 50,
55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200 or more contiguous
nucleotides. In
some embodiments, the marker probe may be used to distinguish (i.e., genotype)
the
particular allele that is present at a marker locus.
As used herein, the terms "marker-assisted selection" and "MAS" refer to a
process by
which phenotypes are indirectly selected based on marker genotypes. MAS can
optionally be
supplemented by direct phenotyping of the trait of interest. For example, when
MAS is used
for breeding, phenotyping can be done at one or more points in the process to
confirm that the
individuals or their progeny express the phenotype of interest
As used herein, the term "marker-assisted counter-selection" refers to a
process by
which marker genotypes are used to identify plants that will not be selected,
allowing them to
be removed from a breeding program or planting.
As used herein, the terms "Ml12.162 plant" and "MIR162 plant part" refer to
maize
plants/plant parts that comprise the MIR162 event as described in U.S. Patent
No. 8,232,456.
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The MIR162 plant or M1R162 plant part can be hemizygous or homozygous for the
MIR162
event.
As used herein, the term "molecular marker" may be used to refer to a genetic
marker,
as defined above, or an encoded product thereof (e.g., a protein) used as a
point of reference
when identifying a linked locus. A molecular marker can be derived from
genomic
nucleotide sequences or from expressed nucleotide sequences (e.g., from a
spliced RNA, a
cDNA, etc.). The term also refers to nucleotide sequences complementary to or
flanking the
marker sequences, such as nucleotide sequences used as probes (as described in
Table 9)
and/or primers capable of amplifying the marker sequence. Nucleotide sequences
are
"complementary" when they specifically hybridize in solution, e.g., according
to Watson-
Crick base pairing rules.
As used herein, the terms "molecule of interest" and "desired molecule" are
used
interchangeably to refer to a haplotype that is linked to a desired trait. A
"molecule of
interest" may be associated with either an increase or decrease of or in a
given trait,
1.5 depending on the nature of the desired phenotype, and may be associated
with a change in
morphology, color, etc. In some embodiments of the present invention, the
"molecule of
interest" is associated with increased male fertility and may therefore be
used as a marker to
identify, select and/or produce fertile maize plants; to predict whether
and/or to what extent a
maize plant will he fertile; to reduce the costs associated with breeding
and/or seed
production programs; and/or to increase the efficiency of breeding and/or seed
production
programs.
As used herein with respect to nucleotides, the term "native" refers to a
nucleic acid
sequence that is naturally present in the genome of a cell or plant.
As used herein with respect to polypeptides, the term "native" refers to an
amino acid
sequence that is naturally present in the proteome of a cell or plant.
As used herein, the terms "near isogenic line" (NIL) and "near isogenic plant"
refer to
m9i7P lines/plants that are genetically identical except for one or a few
genetic loci. Such
lines/plants can be created by crossing a donor line, containing a gene or
trait of interest, with
a recurrent parent to produce a heterozygous Fl, and then repeatedly back-
crossing the
offspring to the recurrent parent (BC1, BC2, etc), retaining the donor gene or
trait in each
successive generation. Marker assisted selection (MAS) can be used to increase
the efficiency
of NIL development by screening individuals for the presence of the target
locus (gene) in
each generation and the absence of extraneous donor DNA throughout the rest of
the genome
to speed up the return to recurrent parent type.
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As used herein, the term "nonnaturally occurring" refers to a plant or plant
part that
does not naturally exist in nature. A nonnaturally occurring plant or plant
part may be
produced by any method known in the art, including, but not limited to,
transforming a plant
or plant part, transfecting a plant or plant part, and crossing a naturally
occurring plant or
plant part with a nonnaturally occurring plant or plant part. In some
embodiments, the
nonnaturally occurring plant or plant part comprises one of more exogenous
nucleotide
sequences. In some embodiments, the nonnaturally occurring plant or plant part
comprises
one or more nonnaturally occurring copies of a naturally occurring nucleotide
sequence (Le.,
additional copies of a gene that naturally occurs in plants/plant parts of
that species that may
be, for example in a nonnatural location in the genome).
As used herein, the terms "nucleic acid," "nucleic acid sequence," "nucleotide
.
sequence" and "polynucleotide" refer to deoxyribonucleotide, ribonucleotide
and
deoxyribonucleotide-ribonucleotide polymers in either single- or double-
stranded form and,
unless otherwise limited, encompasses analogues having the essential nature of
natural
polynucleotides in that they hybridize to single-stranded nucleic acids ins
manner similar to
naturally occurring polynucleotides. Thus, deoxyribopolynucleotides and
ribopolynucleotides that have been chemically, enzymatically or metabolically
modified for
stability or for other reasons and deoxyribopolynucleotides and
ribopolynucleotides
comprising unusual bases (e.g., inosine and/or tritylated bases) are "nucleic
acids" "nucleic
acid sequences" "nucleotide sequences" and "polynucleotides" as those terms
are used herein.
As used herein, the term "nucleotide" refers to a monomeric unit from which
DNA or
RNA polymers arc constructed and that consists of a purine or pyrimidine base,
a pentosc,
and a phosphoric acid group. Nucleotides (usually found in their 5'-
monophosphate form) are
referred to by their single letter designation as follows: "A" for adenylate
or deoxyadenylate
(for RNA or DNA, respectively), "C" for cytidylate or deoxycytidylate, "G" for
guanylate or
deoxyguanylate, "U" for uridylate, "T" for deoxythymidylate, "R" for purines
(A or G), "Y"
for pyrimidines (C or T), "K" for G or T, "H" for A or C or T, "I" for
inosine, and "N" for any
nucleotide.
As used herein, the term "nucleotide sequence identity" refers to the presence
of
identical nucleotides at corresponding positions of two polynucleotides.
Polynucleotides
have "identieal" sequences if the sequence of nucleotides in the two
polynucleotides is the
same when aligned for maximum correspondence (e.g., in a comparison window).
Sequence
comparison between two or more polynucleotides is generally performed by
comparing
portions of the two sequences over a comparison window to identify and compare
local
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regions of sequence similarity. The comparison window is generally from about
20 to 200
contiguous nucleotides. The "percentage of sequence identity" for
polynucleotides, such as
about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, 99 or 100 percent sequence
identity, can be
determined by comparing two optimally aligned sequences over a comparison
window,
wherein the portion of the polynucleotide sequence in the comparison window
can include
additions or deletions (i.e., gaps) as compared to the reference sequence for
optimal
alignment of the two sequences. The percentage is calculated by: (a)
determining the number
of positions at which the identical nucleic acid base occurs in both
sequences; (b) dividing the
number of matched positions by the total number of positions in the window of
comparison;
and (c) multiplying the result by 100. Optimal alignment of sequences for
comparison can
also be conducted by computerized implementations of known algorithms, or by
visual
inspection. Readily available sequence comparison and multiple sequence
alignment
algorithms are, respectively, the Basic Local Alignment Search Tool (BLAST)
and ClustalW
programs, both available on the interne. Other suitable programs include, but
are not limited
to, GAP, BestFit, Plot Similarity, and FASTA, which are part of the Accelrys
GCG Package
available from Accehys, Inc. of San Diego, California, United States of
America. In some
embodiments, a percentage of sequence identity refers to sequence identity
over the full
length of one of the sequences being compared. In some embodiments, a
calculation to
determine a percentage of sequence identity does not include in the
calculation any
nucleotide positions in which either of the compared nucleic acids includes an
"N" (i.e.,
where any nucleotide could be present at that position).
As used herein with respect to nucleic acids, the term "operably linked"
refers to a
functional linkage between two or more nucleic acids. For example, a promoter
sequence
may be described as being "operably linked" to a heterologous nucleic acid
sequence because
the promoter sequences initiates and/or mediates transcription of the
heterologous nucleic
acid sequence. In some embodiments, the operably linked nucleic acid sequences
are
contiguous and/or are in the same reading frame.
As used herein, the terms "phenotype," "phenotypic trait" or "trait" refer to
one or
more traits of an organism. The phenotype can be observable to the naked eye,
or by any
other means of evaluation known in the art, e.g., microscopy, biochemical
analysis, or an
electromechanical assay. In some cases, a phenotype is directly controlled by
a single gene
or genetic locus, i.e., a "single gene trait." In other cases, a phenotype is
the result of several
genes.
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As used herein, the term "plant" may refer to any suitable plant, including,
but not
limited to, spermatophytes (e.g, angiosperms and gymnosperms) and embryophytes
(e.g.,
bryophytes, ferns and fern allies). In some embodiments, the plant is a
monocotyledonous
(monocot) plant such as a rice, maize, wheat, barley, sorghum, millet, oat,
triticale, rye,
buckwheat, fonio, quinoa, sugar cane, bamboo, banana, ginger, onion, lily,
daffodil, iris,
amaryllis, orchid, canna, bluebell, tulip, garlic, secale, einkom, spelt,
emmer, durum, kamut,
grass (e.g., gramma grass), teff, mil, flax, Trzpsacum sp., or teosinte plant.
In some
embodiments, the plant is a dicotyledonous (dicot) plant such as a blackberry,
raspberry,
strawberry, barberry, bearberry, blueberry, coffee berry, cranberry,
crowberry, currant,
elderberry, gooseberry, goji berry, honeyberry, lemon, lime, lingonberry,
tnangosteen,
orange, pepper, persimmon, pomegranate, prune, cotton, clover, acai, plum,
peach, nectarin,
cherry, guava, almond, pecan, walnut, amaranth, apple, sweet pea, pear,
potato, soybean,
sugar beet, sunflower, sweet potato, tamarind, tea, tobacco or tomato plant
As used herein, the term "plant cell" refers to a cell existing in, taken from
and/or
derived from a plant (e.g., derived from a plant cell/tissue culture). Thus,
the term "plant
cell" may refer to an isolated plant cell, a plant cell in a culture, a plant
cell in an isolated
tissue/organ and/or a plant cell in a whole plant.
As used herein, the term "plant part" refers to at least a fragment of a whole
plant or to
a cell culture or tissue culture derived from a plant. Thus, the term "plant
part" may refer to
plant cells, plant tissues and plant organs, as well as cell/tissue cultures
derived from plant
cells, plant tissues and plant cultures. Embodiments of the present invention
may comprise
and/or make use of any suitable plant part, including, but not limited to,
anthers, branches,
buds, calli, clumps, cobs, cotyledons, ears, embryos, filaments, flowers,
fruits, husks, kernels,
leaves, lodicules, ovaries, palea, panicles, pedicels, pods, pollen,
protoplasts, roots, root tips,
seeds, silks, stalks, stems, stigma, styles, and tassels. In some embodiments,
the plant part is
a plant germplasm.
As used herein, the term "polymorphism" refers to a variation in the
nucleotide
sequence at a locus, where said variation is too common to be due merely to a
spontaneous
mutation. A polymorphism generally has a frequency of at least about 1% in a
population. A
polymorphism can be a single nucleotide polymorphism (SNP), or an
insertion/deletion
polymorphism, also referred to herein as an "indel." Additionally, the
variation can be in a
transcriptional profile or a methylation pattern. The polymorphic site or
sites of a nucleotide
sequence can be determined by comparing the nucleotide sequences at one or
more loci in
two or more germplasm entries.
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As used herein, the terms "polypeptide," "peptide" and "protein" refer to a
polymer of
amino acid residues. The terms encompass amino acid polymers in which one or
more amino
acid residue is an artificial chemical analogue of a corresponding naturally
occurring amino
acid, as well as to naturally occurring amino acid polymers.
As used herein, the term "population" refers to a genetically heterogeneous
collection
of plants sharing a common genetic derivation.
As used herein, the term "progeny" refers to plants generated from the
vegetative or
sexual reproduction of one or more parent plants. Progeny plants may be
obtained by cloning
or selling a single parent plant, or by crossing two parental plants. In some
embodiments, the
progeny plants comprise the markers, alleles, haplotypes and/or genomic
regions of the
invention. Depending upon the context, it is not always advantageous that the
progeny
comprise the marker/allele/haplotype/genomic region(s) of the invention
associated with
increased male fertility (e.g, in hybrid production). Thus, in some
embodiments, the progeny
of the invention may not comprise the marker/allele/haplotype/genomic
region(s) of the
invention associated with increased male fertility.
As used herein, the terms "promoter" and "promoter sequence" refer to nucleic
acid
sequences involved in the regulation of transcription initiation. A 'plant
promoter" is a
promoter capable of initiating transcription in plant cells. Exemplary plant
promoters
include, but are not limited to, those that are obtained from plants, plant
viruses and bacteria
that comprise genes expressed in plant cells such Agrobacterium or Rhizobium.
A "tissue-
specific promoter" is a promoter that preferentially initiates transcription
in a certain tissues.
A "stress-inducible promoter" is a promoter that preferentially initiates
transcription under
certain environmental conditions. A "developmental stage-specific promoter" is
a promoter
that preferentially initiates transcription during certain developmental
stages.
As used herein, the term "quantitative trait locus" (QTL) refers to a genetic
locus that
comprises and/or is associated with one or more genes underlying a
quantitative trait.
As used herein, the term "recessive allele" refers to an allele whose
phenotypic effect
is not expressed in a heterozygote.
As used herein, the term "recombinant" refers to a molecule (e.g. DNA, RNA,
protein, etc.) that results from human manipulation, however indirect, of a
nucleic acid
molecule.
As used herein, the term "reference sequence" refers to a defined nucleotide
sequence
used as a basis for nucleotide sequence comparison. The reference sequence for
a marker, for
example, is obtained by genotyping a number of lines at the locus or loci of
interest, aligning
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the nucleotide sequences in a sequence alignment program, and then obtaining
the consensus
sequence of the alignment. Hence, a reference sequence identifies the
polymorphisms in
alleles at a locus. A reference sequence may not be a copy of an actual
nucleic acid sequence
from any particular organism; however, it is useful for designing primers and
probes (as
described in Table 9) for actual polymorphisms in the locus or loci.
As used herein, the term "regulatory element" refers to a nucleotide sequence
involved in controlling the expression of a nucleic acid sequence of interest.
Regulatory
elements comprise a promoter operably linked to the nucleic acid sequence of
interest and
termination signals. They also typically encompass sequences required for
proper translation
of the nucleotide sequence.
As used herein, the terms "selectively hybridize" and "specifically hybridize"
refer to
the hybridization of a nucleic acid sequence to a specified nucleic acid
target sequence,
wherein the nucleic acid sequence preferentially hybridizes to the specified
nucleic acid
target sequence (e.g., at least about a two-fold difference as compared to its
hybridization
with non-target nucleic acid sequences) to the substantial exclusion of non-
target nucleic
acids.
As used herein, the term "stringent hybridization conditions" refers to
conditions
under which a nucleic acid will selectively hybridize to a target nucleic acid
sequence. An
extensive guide to the hybridization of nucleic acids is found in Tijssen,
Laboratory
Techniques in Biochemistry and Molecular Biology-Hybridization with Nucleic
Acid Probes
part I chapter 2 "Overview of principles of hybridization and the strategy of
nucleic acid
probe assays" Elsevier, New York (1993). In some embodiments, stringent
hybridization
conditions comprise 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO4, 1 rnM EDTA
at 50 C
with washing in 0.1x SSC, 0.1% SDS at 65 C. In some embodiments, stringent
hybridization
conditions comprise a wash stringency of 50% fonnamide with 5x Denhardt's
solution, 0.5%
SDS and lx SSPE at 42 C. Typically, under "stringent conditions" a probe will
hybridize to
its target subsequence, but to no other sequences.
As used herein, "T." refers to the temperature (under defined ionic strength
and pH)
at which 50% of the target sequence hybridizes to a perfectly matched probe.
Very stringent
conditions are selected to be equal to the T. for a particular probe. An
example of stringent
hybridization conditions for hybridization of complementary nucleic acids
which have more
than 100 complementary residues on a filter in a Southern or northern blot is
50% formamide
with 1 mg of heparin at 42 C, with the hybridization being carried out
overnight An
example of highly stringent wash conditions is 0.1 5M NaCl at 72 C for about
15 minutes.
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An example of stringent wash conditions is a 0.2x SSC wash at 65 C for 15
minutes (see,
Sambrook, infra, for a description of SSC buffer). Often, a high stringency
wash is preceded
by a low stringency wash to remove background probe signal. An example medium
stringency wash for a duplex of, e.g., more.than la) nucleotides, is lx SSC at
45 C for 15
minutes. An example low stringency wash for a duplex of, e.g., more than 100
nucleotides, is
4-6x SSC at 40 C for 15 minutes. For short probes (e.g., about 10 to 50
nucleotides), stringent
conditions typically involve salt concentrations of less than about 1.0 M Na
ion, typically
about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3,
and the temperature
is typically at least about 30 C. Stringent conditions can also be achieved
with the addition of
destabilizing agents such as formamide. In general, a signal to noise ratio of
2x (or higher)
than that observed for an unrelated probe in the particular hybridization
assay indicates
detection of a specific hybridization. Nucleic acids that do not hybridize to
each other under
stringent conditions are still substantially identical if the proteins that
they encode are
substantially identical. This occurs, e.g., when a copy of a nucleic acid is
created using the
maximum codon degeneracy permitted by the genetic code.
The following are examples of sets of hybridization/wash conditions that may
be used
to clone homologous nucleotide sequences that are substantially identical to
reference
nucleotide sequences of the present invention: 7% sodium dodecyl sulfate
(SDS), 0.5 M
NaPO4, 1 mM EDTA at 50 C with washing in 2X SSC, 0.1% SDS at 50 C; 7% sodium
dodecyl sulfate (SDS), 0.5 M NaPO4, 1 mM EDTA at 50 C with washing in IX SSC,
0.1%
SDS at 50 C; 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO4, 1 mM EDTA at 50 C
with
washing in 0.5X SSC, 0.1% SDS at 50 C; 7% sodium dodecyl sulfate (SDS), 0.5 M
NaPO4,
1 mM EDTA at 50 C with washing in 0.1X SSC, 0.1% SDS at 50 C; 7% sodium
dodecyl
sulfate (SDS), 0.5 M NaPO4, 1 mM EDTA at 50 C with washing in 0.1X SSC, 0.1%
SDS at
65 C.
A further indication that two nucleic acid sequences or proteins are
substantially
identical is that the protein encoded by the first nucleic acid is
immunologically cross reactive
with, or specifically binds to, the protein encoded by the second nucleic
acid. Thus, a protein
is typically substantially identical to a second protein, for example, where
the two proteins
differ only by conservative substitutions.
As used herein, the term "substantially fertile" refers to a plant whose
fertility is
substantially the same as that of a control plant (e.g., one or both of its
parents, a near
isogenic plant that lacks one or more markers/alleles associated with
increased fertility, a near
isogenic plant that lacks a vip3 coding sequence, etc.). In some embodiments,
substantially
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fertile plants are plants that release pollen grains at a per tassel per day
rate that is at least
about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of that of the control in
the three-
day period immediately following anther extrusion. In some embodiments,
"substantially
fertile" plants are plants that release at least about 500,000; 600,000;
700,000; 800,000;
900,000; or 1,000,000 pollen grains per tassel per day in the three-day period
immediately
following anther extrusion.
As used herein, the phrase TAQMA1N Assay" refers to real-time sequence
detection
using PCR based on the TAQMANe Assay sold by Applied Biosystems, Inc. of
Foster City,
California, United States of America. For an identified marker, a TAQMANe
Assay can be
developed for application in a breeding program.
As used herein, the terms "transformation", "transfection" and "transduction"
refer to
the introduction of an exogenous/heterologous nucleic acid (RNA and/or DNA)
into a host
cell. A cell has been "transformed," "transfected" or "transduced" with an
exogenous/heterologous nucleic acid when such nucleic acid has been introduced
or
delivered into the cell.
As used herein, the terms "transgenic" and "recombinant" refer to an organism
(e.g., a
bacterium or plant) that comprises one or more exogenous nucleic acids.
Generally, the
exogenous nucleic acid is stably integrated within the genome such that at
least a portion of
the exogenous nucleic acid is passed on to successive generations. The
exogenous nucleic
acid may be integrated into the genome alone or as part of a recombinant
expression cassette.
"Transgenic" may be used to designate any plant or plant part the genotype of
which has been
altered by the presence of an exogenous nucleic acid, including those
transgenics initially so
altered and those created by sexual crosses or asexual propagation from the
initial transgenie.
As used herein, the term "transgenic" does not encompass the alteration of the
genome
(chromosomal or extra-chromosomal) by conventional plant breeding methods or
by
naturally occurring events such as random cross-fertilization, non-recombinant
viral
infection, non-recombinant bacterial transformation, non-recombinant
transposition or
spontaneous mutation.
Transformation of a cell may be stable or transient. Thus, in some
embodiments, a
plant cell of the invention is stably transformed with a nucleotide sequence
encoding a
synthetic miRNA precursor molecule of the invention. In other embodiments, a
plant of the
invention is transiently transformed with a nucleotide sequence encoding a
synthetic miRNA
precursor molecule of the invention.
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"Transient transformation" in the context of a polynucleotide means that a
polynucleotide is introduced into the cell and does not integrate into the
genome of the cell.
"Stable transformation" or "stably transformed," "stably introducing," or
"stably
introduced" as used herein means that a nucleic acid is introduced into a cell
and integrates
into the genome of the cell. As such, the integrated nucleic acid is capable
of being inherited
by the progeny thereof, more particularly, by the progeny of multiple
successive generations.
"Genome" as used herein also includes the nuclear and the plastid genome, and
therefore
includes integration of the nucleic acid into, for example, the chloroplast
genome. Stable
transformation as used herein can also refer to a transgene that is maintained
extrachromasomally, for example, as a rnimichromosome.
As used herein, the term "transgene" refers to an exogenous nucleic acid.
Transgenes
may be single- or double-stranded.
As used herein with respect to plants and plant parts, the term "transgenic"
refers to a
plant or plant part that comprises one or more exogenous nucleic acids.
As used herein, the term "unfavorable allele" refers to a marker allele that
segregates
with an unfavorable plant phenotype, therefore providing the benefit of
identifying plants that
can be removed from a breeding program or planting.
As used herein, the term "vector" refers to a nucleic acid molecule for the
cloning of
and/or transfer of a nucleic acid into a cell. A vector may be a replicon to
which another
nucleotide sequence may be attached to allow for replication of the attached
nucleotide
sequence. A "replic.on" can be any genetic element (e.g., plasmid, phage,
cosmid,
chromosome, viral gcnome) that functions as an autonomous unit of nucleic acid
replication
in vivo (i.e., is capable of replication under its own control). The term
"vector" includes both
viral and nonviral (e.g., plasmid) nucleic acid molecules for introducing a
nucleic acid into a
cell in vitro, ex vivo, and/or in vivo. A large number of vectors known in the
art may be used
to manipulate nucleic acids, incorporate response elements and promoters into
genes, etc.
For example, the insertion of nucleic acid fragments corresponding to response
elements and
promoters into a suitable vector can be accomplished by ligating the
appropriate nucleic acid
fragments into a chosen vector that has complementary cohesive termini.
Alternatively, the
ends of the nucleic acid molecules may be enzymatically modified or any site
may be
produced by ligating nucleotide sequences (linkers) to the nucleic acid
termini. Such vectors
may be engineered to contain sequences encoding selectable markers that
provide for the
selection of cells that contain the vector and/or have incorporated the
nucleic acid of the
vector into the cellular genome. Such markers allow for the identification
and/or selection of
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cells that incorporate and express the proteins encoded by the marker. A
"recombinant"
vector refers to a viral or non-viral vector that comprises one or more
heterologous nucleotide
sequences (i.e., transgenes). Vectors may be introduced into cells by any
suitable method
known in the art, including, but not limited to, transfection,
electroporation, microinjection,
transduction, cell fusion, DEAE dextran, calcium phosphate precipitation,
lipofection
(lysosome fusion), and use of a gene gun or nucleic acid vector transporter.
As used herein, the term "Vip3 protein" refers to a vegetative insecticidal
protein
(VIP) that is a member of the Vip3 class of proteins and includes, but is not
limited to,
Vip3A(a), Vip3A(b), Vip3A(c), Vip3B, Vip3C(a), Vip3C(b)and Vip3Z proteins and
their
homologues. Homologues of the aforementioned members of the Vip3 class of
proteins
include, but are not limited to, proteins that are cross-reactive with
antibodies that
immunologically recognize one or more of the aforementioned member of the Vip3
class of
proteins, proteins that are cross-reactive with receptors (e.g., on a nematode
pest or insect
gut) affected by one or more of the aforementioned member of the Vip3 class of
proteins,
proteins having an amino acid sequence that is at least about 70, 71, 72, 73,
74, 75, 76, 77,
78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,
97, 98, 99% or more
similar or identical to one or more of the aforementioned member of the Vip3
class of
proteins, and proteins having a toxic core region, the amino acid sequence of
which is at least
about 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,
88, 89, 90, 91, 92,
93, 94, 95, 96, 97, 98, 99% or more similar or identical to the toxic core
region of one or
more of the aforementioned member of the Vip3 class of proteins. Homologues of
the
aforementioned members of the Vip3 class of proteins may exhibit pesticidal
activity (e.g.,
nematicidal and/or insecticidal) when expressed in a transgenic maize plant or
plant part.
Examples of Vip3 proteins (and corresponding GenBank accession numbers and/or
U.S.
patent publication numbers) are described in Table 4.
Markers can be used in a variety of plant breeding applications. See, e.g.,
Staub et at.,
Hortscience 31: 729(1996); Tanksley, Plant Molecular Biology Reporter 1: 3
(1983). One
of the main areas of interest is to increase the efficiency of backcrossing
and introgressing
genes using marker-assisted selection (MAS). In general, MAS takes advantage
of genetic
markers that have been identified as having a significant likelihood of co-
segregation with a
desired trait. Such markers are presumed to be in/near the gene(s) that give
rise to the desired
phenotype, and their presence indicates that the plant will possess the
desired trait. Plants
which possess the marker are expected to transfer the desired phenotype to
their progeny.
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A marker that demonstrates linkage with a locus affecting a desired phenotypic
trait
provides a useful tool for the selection of the trait in a plant population.
This is particularly
true where the phenotype is hard to assay or occurs at a late stage in plant
development.
Since DNA marker assays are less laborious and take up less physical space
than field
phenotyping, much larger populations can be assayed, increasing the chances of
finding a
recombinant with the target segment from the donor line moved to the recipient
line. The
closer the linkage, the more useful the marker, as recombination is less
likely to occur
between the marker and the gene causing or imparting the trait. Having
flanking markers
decreases the chances that false positive selection will occur. The ideal
situation is to have a
marker in the gene itself, so that recombination cannot occur between the
marker and the
gene. Such a marker is called a "perfect marker."
When a gene is introgressed by MAS, it is not only the gene that is introduced
but
also the flanking regions. Gepts, Crop Sci. 42:1780(2002). This is referred to
as "linkage
drag." In the case where the donor plant is highly unrelated to the recipient
plant, these
flanking regions carry additional genes that may code for agronomically
undesirable traits.
This "linkage drag" may also result in reduced yield or other negative
agronomic
characteristics even after multiple cycles of backcrossing into the elite
maize line. This is
also sometimes referred to as "yield drag." The size of the flanking region
can be decreased
by additional backcrossing, although this is not always successful, as
breeders do not have
control over the size of the region or the recombination breakpoints. Young et
al., Genetics
120:579 (1998). In classical breeding, it is usually only by chance that
recombinations which
contribute to a reduction in the size of the donor segment are selected.
Tanksley et al.,
Biotechnology 7: 257 (1989). Even after 20 backcrosses, one may expect to find
a sizeable
piece of the donor chromosome still linked to the gene being selected. With
markers,
however, it is possible to select those rare individuals that have experienced
recombination
near the gene of interest. In 150 backcross plants, there is a 95% chance that
at least one
plant will have experienced a crossover within 1 cM of the gene, based on a
single meiosis
map distance. Markers allow for unequivocal identification of those
individuals. With one
additional backcross of 300 plants, there would be a 95% chance of a crossover
within 1 cM
single meiosis map distance of the other side of the gene, generating a
segment around the
target gene of less than 2 cM based on a single meiosis map distance. This can
be
accomplished in two generations with markers, while it would have required on
average 100
generations without markers. See Tanksley et al., supra. When the exact
location of a gene is
known, flanking markers surrounding the gene can be utilized to select for
recombinations in
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different population sizes. For example, in smaller population sizes,
recombinations may be
expected further away from the gene, so more distal flanking markers would be
required to
detect the recombination.
The availability of integrated linkage maps of the maize genome containing
increasing densities of public maize markers has facilitated maize genetic
mapping and MAS.
See, e.g. the IBM2 Neighbors maps, which are available online on the MaizeGDB
website.
Of all the molecular marker types, SNPs are the most abundant and have the
potential
to provide the highest genetic map resolution. Bhattramakki et al., Plant
Molec. Biol. 48:539
(2002). SNPs can be assayed in a so-called "ultra-high-throughput" fashion
because they do
not require large amounts of nucleic acid and automation of the assay is
straight-forward.
SNPs also have the benefit of being relatively low-cost systems. These three
factors together
make SNPs highly attractive for use in MAS. Several methods are available for
SNP
genotyping, including but not limited to, hybridization, primer extension,
oligonucleotide
ligation, nuclease cleavage, minisequeneing and coded spheres. Such methods
have been
reviewed in various publications: Gut, Hum. Mutat. 17:475 (2001); Shi, Clin.
Chem. 47:164
(2001); Kwok, Pharmacogenomics 1:95 (2000); Bhattramakki and Rafalski,
Discovery and
application of single nucleotide polymorphism markers in plants, in PLANT
GENorvPiNG:
Tim DNA FINCiERPIUNTRYG OF PLANTS, CABI Publishing, Wallingford (2001). A wide
range
of commercially available technologies utilize these and other methods to
interrogate SNPs,
including MasscodeTm (Qiagen, Germantown, MD), Invader (Hologic, Madison, WI),
SnapShoe (Applied Biosystems, Foster City, CA), Taqman6 (Applied Biosystems,
Foster
City, CA) and BeadarraysTm (Illumina, San Diego, CA).
A number of SNPs together within a sequence, or across linked sequences, can
be
used to describe a haplotype for any particular genotype. Ching et al., BMC
Genet. 3:19
(2002); Gupta et al., (2001), Rafalski, Plant Scl 162:329 (2002b). Haplotypes
can be more
informative than single SNPs and can be more descriptive of any particular
genotype. For
example, a single SNP may be allele "T" for a specific donor line or variety,
but the allele "T"
might also occur in the maize breeding population being utilized for recurrent
parents lacking
the favorable allele. In this case, a combination of alleles at linked SNPs
may be more
informative. Once a unique haplotype has been assigned to a donor chromosomal
region, that
haplotype can be used in that population or any subset thereof to determine
whether an
individual has a particular gene. The use of automated high throughput marker
detection
platforms known to those of ordinary skill in the art makes this process
highly efficient and
effective.
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The present invention provides markers associated with increased fertility
(e.g.,
increased male fertility). Analysis of these markers can be used to identify,
select and/or
produce fertile maize plants, to identify infertile maize plants, to predict
whether and/or to
what extent a maize plant will be fertile, to increase the efficiency of
and/or reduce the cost of
breeding and/or seed production programs, etc.
Markers of the present invention may comprise, consist essentially of or
consist of a
single allele or a combination of alleles at one or more genetic loci. For
example, the marker
may comprise a marker allele located at a first marker locus, a marker allele
at a second
marker locus, a marker allele at a third marker locus, a fourth marker at a
fourth marker
locus, etc.
In some embodiments, the marker is located within one or more of the
chromosomal
segments described in Table 1 as if each interval and all possible
combinations thereof were
individually set forth. For example, the marker may be located within one or
more of
chromosomal segments 46 to 12473 (e.g., within chromosomal segment 7514).
In some embodiments, the marker comprises, consists essentially of or consists
of an
allele of interest located within one or more of the chromosomal segments
described in Table
1. For example, in some embodiments, the marker comprises, consists
essentially of or
consists of an allele of interest located within one or more of chromosomal
segments 46 to
12473 (e.g., an allele of interest located within chromosomal segment 7514).
In some embodiments, the marker comprises, consists essentially of or consists
of a
haplotype comprising, consisting essentially of, or consisting of two or more
alleles of
interest located within one or more of the chromosomal segments described in
Table 1. For
example, in some embodiments, the marker comprises, consists essentially of or
consists of a
haplotype comprising, consisting essentially of, or consisting of two or more
alleles of
interest located within one or more of chromosomal segments 46 to 12473 (e.g.,
a haplotype
comprising two or more alleles of interest located within chromosomal segment
7514).
In some embodiments, the marker comprises, consists essentially of or consists
of a
haplotype comprising, consisting essentially of, or consisting of one or more
alleles of
interest located within a first chromosomal segment, one or more alleles of
interest located
within a second chromosomal segment different from the first chromosomal
segment, one or
more alleles of interest located within a third chromosomal segment different
from the first
and second chromosomal segments, etc., wherein each of the chromosomal
segments
comprises one or more of the chromosomal segments described in Table I. For
example, in
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some embodiments, the marker comprises, consists essentially of or consists of
a haplotype
comprising, consisting essentially of, or consisting of:
1) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g. one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
1;
2) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located on chromosome 2;
3) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3);
4) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 18 to 45 (e.g., one or more alleles of interest located within
chromosomal
segment 25);
5) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal segment 12747);
6) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal segment 12753);
7) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
12756;
8) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
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segments 12757 to 12762 (e.g., one or more alleles of interest located within
chromosomal segment 12760 and/or chromosomal segment 12761);
9) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal segment 12768);
10) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514), one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3), one or more alleles of interest located within one or more of
chromosomal segments 18 to 45 (e.g., one or more alleles of interest located
within
chromosomal segment 25) and one or more alleles of interest located within one
or
more of chromosomal segments 12763 to 12768 (e.g., one or more alleles of
interest
located within chromosomal segment 12768);
11)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within chromosomal segment 1;
12) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located on chromosome 2;
13) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
18 to 45 (e.g., one or more alleles of interest located within chromosomal
segment
25);
14)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal
segment 12747);
15)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
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one or more alleles of interest located within one or more of chromosomal
segments
12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal
segment 12753);
16) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g, one or more alleles of interest located within chromosomal segment
3) and
one or more alleles of interest located within chromosomal segment 12756;
17) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12757 to 12762 (e.g., one or more alleles of interest located within
chromosomal
segment 12760 and/or chromosomal segment 12761);
18)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal
segment 12768);
19)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3),
one or more alleles of interest located within one or more of chromosomal
segments
12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal
segment 12753) and one or more alleles of interest located within chromosomal
segment 12756.
In embodiments, the marker comprises one or more of the desired alleles
described in
Table 8. For example, in some embodiments, the marker comprises at least about
2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or more, or all 18 of the desired
alleles described in
Table 8.
In embodiments, the marker comprises one or more of the favorable (desired)
alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
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(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In embodiments, the marker comprises one or more of the favorable (desired)
alleles
described in Table 10.
In some embodiments, the marker comprises, consists essentially of or consists
of one
or more marker alleles linked to one or more of the markers, chromosomal
segments, alleles
and/or haplotypes described herein. In some embodiments, the marker allele and
the
marker(s), segment(s), allele(s) and/or haplotype(s) described herein are
separated by less
than about 50, 40, 30, 25, 20, 15, 10, 5, 4, 3, 2, or 1 cM. In some
embodiments, the pairwise
r2 value(s) of the marker allele and the
marker(s)/segment(s)/allele(s)/haplotype(s) described
herein is/are greater than or equal to about 0.33, 0.4,0.5, 0.6, 0.7,0.8, 0.9,
or 1Ø In some
embodiments, the LOD score for the marker allele and the
marker(s)/segment(s)/allele(s)/haplotype(s) described herein is greater than
or equal to about
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4,4.5, 5. 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5,
10, 11, 12, 13, 14, 15, 16,
17, 18, 19,20 or more. Linked markers may be determined, for example, by using
resources
available on the MaizeGDB website (www.maizegdb.org).
In some embodiments, the marker comprises, consists essentially of or consists
of a
marker allele located within about 25cM, 20 cM, 15 cM, 10 cM, 5 cM or 1 cM or
less (the
term "within" including the end point of the specified region) of any one of
the markers,
chromosomal segments, alleles and/or haplotypes described herein. For example,
in some
embodiments, the marker allele comprises, consists essentially of or consists
of one or more
markers located within about 25 cM, 10cM, 5 cM, 1cM or less of chromosomal
segment
7514.
In some embodiments, the marker is not in the natural genetic background of
the
maize plant (e.g., is not naturally occurring in the maize line or variety,
and has been
introduced therein by human intervention).
Markers of the present invention may associated with any suitable trait,
including, but
not limited to, increased pollen production per plant, increased pollen
production per tassel,
increased pollen production per anther, improved pollen morphology, increased
anther
production per plant, increased anther production per tassel, improved anther
morphology,
increased tassel production per plant, improved tassel morphology, increased
fertility (e.g.,
increased male fertility) under stress conditions (e.g., drought conditions),
increased fertility
(e.g., increased male fertility) under elevated daytime temperatures,
increased fertility (e.g.,
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increased male fertility) under elevated nighttime temperatures and/or
increased fertility (e.g.,
increased male fertility) under conditions comprising a large differential
between daytime
temperatures and nighttime temperatures.
Markers of the present invention may be analyzed using any suitable marker
probe,
including, but not limited to, the marker probes described herein.
Markers of the present invention may be detected in any suitable amplification
product, including, but not limited to, the amplification products described
herein.
Markers of the present invention may be analyzed using any suitable
technique(s),
including, but not limited to, PCR-based detection methods (e.g., TAQMAN
Assays),
polymorphism detection techniques (see, e.g., U.S. Patent Nos. 5,468,613,
5,217,863;
5,210,015; 5,876,930; 6,030,787; 6,004,744; 6,013,431; 5,595,890; 5,762,876;
5,945,283;
5,468,613; 6,090,558; 5,800,944; 5,616,464; 7,312,039; 7,238,476; 7,297,485;
7,282,355;
7,270,981 and 7,250,252), probe ligation techniques (see, e.g., U.S. Patent
No. 5,800,944),
microarray techniques (see, e.g., U.S. Patent Nos. 6,799,122; 6,913,879 and
6,996,476; see
also Borevitz et al., GENOME RES. 13:513-523 (2003); Cui et al.,
BIOINFORMATICS 21:3852-
3858 (2005)), probe linking methods (e.g., U.S. Patent No. 5,616,464), single
base extension
methods (see, e.g., U.S. Patent Nos. 6,004,744; 6,013,431; 5,595,890;
5,762,876 and
5,945,283), fluorescent tagging methods (e.g., U.S. Patent Nos. 5,210,015;
5,876,930 and
6,030,787) and direct sequencing (see, e.g., Service, SCIENCE 2006 311:1544-
1546(2006)).
The present invention also provides nonnaturally occurring plants and plant
parts
comprising one or more markers associated with increased fertility (e.g.,
increased male
fertility).
The present invention extends to products harvested from nonnaturally
occurring
plants of the present invention, including, but not limited to, plant cells
and harvestable plant
parts including but not limited to seeds, leaves, fruits, flowers, stems,
rhizomes, tubers and
bulbs.
In some embodiments, the harvested product can be a plant cell or plant part
capable
of producing a plant having increased fertility (e.g., increased male
fertility).
The present invention also extends to products derived from nonnaturally
occurring
plants and plant parts of the present invention, including, but not limited
to, dry pellets and
powders, oils, fats, fatty acids, starches and proteins.
Markers and nonnaturally occurring plants and plant parts of the present
invention
may comprise any suitable allele(s), haplotype(s) and/or molecule(s) of
interest.
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In some embodiments, the allele of interest comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from NP2222 maize
germplasm. For
example, the alleles of interest may comprise, consist essentially of or
consist of one or more
of the chromosomal segments described in Table 1, wherein the chromosomal
segment is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the corresponding segment(s) of NP2222 maize germplasm. In some such
embodiments, the
allele of interest comprises, consists essentially of or consists of one or
more of chromosomal
segments 3 to 12768, (e.g., chromosomal segments 3, 13, 25, 506, 7514, 7546,
12747, 12753,
12760-12761 and/or 12767-12768) of NP2222 maize germplasm.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from NP2660 maize
germplasm. For
example, the alleles of interest may comprise, consist essentially of or
consist of one or more
of the chromosomal segments described in Table 1, wherein the chromosomal
segment is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the corresponding segment(s) of NP2660 maize germplasm. In some such
embodiments, the
allele of interest comprises, consists essentially of or consists of one or
more of chromosomal
segments 3 to 12743 and/or one or more of chromosomal segments 12757 to 12768,
(e.g.,
chromosomal segments 3, 13, 25, 506, 7514, 7546, 12747, 12753, 12760-12761
and/or
12767-12768) of NP2660 maize germplasm.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from NP2276 maize
germplasm. For
example, the alleles of interest may comprise, consist essentially of or
consist of one or more
of the chromosomal segments described in Table 1, wherein the chromosomal
segment is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the corresponding segment(s) of NP2276 maize germplasm. In some such
embodiments, the
allele of interest comprises, consists essentially of or consists of
chromosomal segment 1, one
or more of chromosomal segments 46 to 12743 and/or one or more of chromosomal
segments
12757 to 12768, (e.g., chromosomal segments 13, 506, 7514, 7546 and/or 12760-
12761) of
NP2276 maize germplasm.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from ID3461 maize
germplasm. For
example, the alleles of interest may comprise, consist essentially of or
consist of one or more
of the chromosomal segments described in Table I, wherein the chromosomal
segment is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
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the corresponding segment(s) of 11)3461 maize germplasm. In some such
embodiments, the
allele of interest comprises, consists essentially of or consists of one or
more of chromosomal
segments I to 17 (e.g., chromosomal segments 1 and/or 13) of ID3461 maize
gennplasm.
In embodiments, the allele of interest comprises, consists essentially of or
consists of
one or more nucleic acid sequences derived from a line in Table 11.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one of SEQ ID NOs: Ito 350 (as described in Table 3).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that is at least about 75%, 80%,
85%, 90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 1 to
350 (as
described in Table 3).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that specifically hybridizes to
the nucleotide
sequence of one or more of SEQ ID NOs: 1 to 350 (as described in Table 3)
under stringent
hybridization conditions.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that encodes the amino acid
sequence set forth in
one or more of SEQ ID NOs: 351 to 525 (as described in Table 3).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that encodes an amino acid
sequence that is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the amino acid sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as
described in
Table 3).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one of SEQ ID NOs: 526 to 613 (as described in Table 9).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that is at least about 75%, 80%,
85%, 90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 526
to 613
(as described in Table 9).
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of at least one nucleotide sequence that specifically hybridizes to
the nucleotide
sequence of one or more of SEQ ID NOs: 526 to 613 (as described in Table 9)
under
stringent hybridization conditions.
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In some embodiments, the allele of interest comprises, consists essentially of
or
consists of one or more of the desired alleles described in Table 2. For
example, in some
embodiments, the marker comprises, consists essentially of or consists of at
least about 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,
65, 70, 75, 80, 85, 90,
95, 100, 110, 120, 130, 140 or more of the desired alleles described in Table
2.
In embodiments, the allele of interest comprises one or more of the desired
alleles
described in Table 8. For example, in some embodiments, the marker comprises
at least
about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or more, or all
18 of the desired
alleles described in Table 8.
In embodiments, the allele of interest comprises one or more of the desired
alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In embodiments, the allele of interest comprises one or more of the desired
alleles
described in Table 10. For example, in some embodiments, the marker comprises
at least
about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20,25 or more of the
desired alleles
described in Table 10.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of the reverse complement of one of the alleles of interest described
herein.
In some embodiments, the allele of interest comprises, consists essentially of
or
consists of an informative fragment of one of the alleles of interest
described herein.
In some embodiments, the allele of comprises, consists essentially of or
consists of an
informative fragment of the reverse complement of one of the alleles of
interest described
herein.
In some embodiments, the allele of interest is not in the natural genetic
background of
the maize plant (e. g. , is not naturally occurring in the maize line or
variety, and has been
introduced therein by human intervention).
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In some embodiments, the haplotype of interest comprises, consists essentially
of or
consists of nucleic acid sequences derived from NP2222 maize germplasm. For
example, the
haplotype of interest may comprise, consist essentially of or consist of one
or more (or two or
more) of the chromosomal segments described in Table 1, wherein the
chromosomal segment
is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical
to the corresponding segment(s) of NP2222 maize germplasm. In some such
embodiments,
the haplotype of interest comprises one or more nucleic acid sequences is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more
of
chromosomal segments 3 to 12768, (e.g., chromosomal segments 3, 13, 25, 506,
7514, 7546,
12747, 12753, 12760-12761 and/or 12767-12768) of NP2222 maize germplasm.
In some embodiments, the haplotype of interest comprises, consists essentially
of or
consists of nucleic acid sequences derived from NP2660 maize germplasm. For
example, the
haplotype of interest may comprise, consist essentially of or consist of one
or more (or two or
more) of the chromosomal segments described in Table 1, wherein the
chromosomal segment
is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical
to the corresponding segment(s) of NP2660 maize germplasm. In some such
embodiments,
the haplotype of interest comprises one or more nucleic acid sequences is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more
of
chromosomal segments 3 to 12743 and/or one or more of chromosomal segments
12757 to
12768, (e.g., chromosomal segments 3, 13, 25, 506, 7514, 7546, 12747, 12753.
12760-12761
and/or 12767-12768) of NP2660 maize germplasm.
In some embodiments, the haplotype of interest comprises, consists essentially
of or
consists of nucleic acid sequences derived from NP2276 maize germplasm. For
example, the
haplotype of interest may comprise, consist essentially of or consist of one
or more (or two or
more) of the chromosomal segments described in Table 1, wherein the
chromosomal segment
is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical
to the corresponding segment(s) of NP2276 maize germplasm. In some such
embodiments,
the haplotype of interest comprises one or more nucleic acid sequences is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to chromosomal
segment 1, one or more of chromosomal segments 46 to 12743 and/or one or more
of
chromosomal segments 12757 to 12768, (e.g., chromosomal segments 13, 506,
7514, 7546
and/or 12760-12761) of NP2276 maize germplasm.
In some embodiments, the haplotype of interest comprises, consists essentially
of, or
consists of nucleic acid sequences derived from ID3461 maize germplasm. For
example, the
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haplotype of interest may comprise, consist essentially of or consist of one
or more (or two or
more) of the chromosomal segments described in Table 1, wherein the
chromosomal segment
is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical
to the corresponding segment(s) of ID3461 maize gemmlasm. In some such
embodiments,
the haplotype of interest comprises one or more nucleic acid sequences is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more
of
chromosomal segments 1 to 17 (e.g., chromosomal segments 1 and/or 13) of
ID3461 maize
germplasm.
In embodiments, the haplotype of interest comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from a line in Table
11.
In some embodiments, the haplotype of interest comprises one or more of the
nucleic
acid sequences set forth in SEQ ID NOs: 1 to 350 (as described in Table 3).
hi some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences that is/are at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to one or more of SEQ D NOs: 1 to 350 (as
described in
Table 3).
In some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences that specifically hybridize to the nucleotide
sequence of one or
more of SEQ ID NOs: Ito 350 (as described in Table 3) under stringent
hybridization
conditions.
In some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences encoding the amino acid sequence set forth in one
or more of
SEQ ID NOs: 351 to 525 (as described in Table 3).
In some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences encoding an amino acid sequence that is at least
about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to the amino
acid
sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as described in
Table 3).
In some embodiments, the haplotype of interest comprises one or more (or two
or
more) of the nucleic acid sequences set forth in SEQ ID NOs: 526 to 613 (as
described in
Table 9).
In some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences that is/are at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 526 to 613 (as
described
in Table 9).
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In some embodiments, the haplotype of interest comprises one or more (or two
or
more) nucleotide sequences that specifically hybridize to the nucleotide
sequence of one or
more of SEQ ID NOs: 526 to 613 (as described in Table 9) under stringent
hybridization
conditions.
In some embodiments, the haplotype of interest comprises one or more of the
desired
alleles described in Table 2. For example, in some embodiments, the haplotype
of interest
comprises, consists essentially of or consists of at least about 2, 3, 4, 5,
6, 7, 8,9, 10, 11, 12,
13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,
100, 110, 120, 130,
140 or more of the desired alleles described in Table 2.
In embodiments, the haplotype of interest comprises one or more of the desired
alleles
described in Table 8. For example, in some embodiments, the haplotype of
interest
comprises at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,
17 or more, or all 18
of the desired alleles described in Table 8.
In embodiments, the haplotype of interest comprises one or more (or two or
more) of
the desired allele(s):
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(I) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In embodiments, the haplotype of interest comprises one or more (or two or
more) of
the desired alleles described in Table 10. For example, in some embodiments,
the haplotype
of interest comprises at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13,
14, 15, 20,25 or more
of the desired alleles described in Table 10.
In some embodiments, the haplotype of interest comprises the reverse
complement of
one or more (or two or more) of the alleles of interest described herein. For
example, in some
embodiments, at least one allele of interest in a haplotype of interest is
present as described
herein, whilst at least one other allele of interest in the haplotype of
interest is present as the
reverse complement of the allele(s) described herein.
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In some embodiments, the haplotype of interest comprises an informative
fragment of
one or more (or two or more) of the alleles of interest described herein. For
example, in some
embodiments, at least one allele of interest in a haplotype of interest is
present as described
herein, whilst at least one other allele of interest in the haplotype of
interest is present as an
informative fragment of the allele(s) described herein.
In some embodiments, the haplotype of interest comprises an informative
fragment of
the reverse complement of one or more (or two or more) of the alleles of
interest described
herein. For example, in some embodiments, at least one allele of interest in a
haplotype of
interest is present as described herein, whilst at least one other allele of
interest in the
haplotype of interest is present as an informative fragment of the reverse
complement of the
allele(s) described herein.
In some embodiments, the molecule of interest comprises, consists essentially
of or
consists of at least one of SEQ ID NOs: 351 to 525 (as described in Table 3).
In some embodiments, the molecule of interest comprises, consists essentially
of or
consists of at least one amino acid sequence that is at least about 75%, 80%,
85%, 90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 351
to 525
(as described in Table 3).
In some embodiments, the molecule of interest is not in the natural proteome
of the
maize plant (e.g., is not naturally occurring in the maize line or variety,
and has been
introduced therein by human intervention).
In some embodiments, the allele/haplotype/molecule of interest is associated
with
increased pollen production per plant, increased pollen production per tassel,
increased pollen
production per anther, improved pollen morphology, increased anther production
per plant,
increased anther production per tassel, improved anther morphology, increased
tassel
production per plant, improved tassel morphology, increased fertility (e.g.,
increased male
fertility) under stress conditions (e.g., drought conditions), increased
fertility (e.g., increased
male fertility) under elevated daytime temperatures, increased fertility
(e.g., increased male
fertility) under elevated nighttime temperatures and/or increased fertility
(e.g., increased male
fertility) under conditions comprising a large differential between daytime
temperatures and
nighttime temperatures.
Markers and nonnaturally occurring plants and plant parts of the present
invention
may comprise any suitable number of alleles, haplotypes and/or molecules of
interest as
described herein.
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=
In some embodiments, the marker/nonnaturally occurring plant or plant part
comprises at least 2, 3,4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 20, 25, 30,
35, 40, 45, 50, 55, 60,
65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140 or more alleles,
haplotypes and/or
molecules of interest associated with increased fertility (e.g., increased
male fertility) as
described herein. For example, in some such embodiments, the
marker/nonnaturally
occurring plant or plant part comprises at least 2, 3,4, 5, 6, 7, 8, 9, 10,
11, 12, 13,14, 15, 20,
25, 30, 35, 40, 45, 50, 55, 60, 65, 70,75, 80, 85, 90, 95, 100, 110, 120, 130,
140 or more
alleles, haplotypes, molecules of interest (as described herein) associated
with increased
pollen production, increased pollen production per tassel, increased pollen
production per
anther, improved pollen morphology, increased anther production per plant,
increased anther
production per tassel, improved anther morphology, increased tassel production
per plant,
improved tassel morphology, increased fertility (e.g., increased male
fertility) under stress
conditions (e.g., drought conditions), increased fertility (e.g., increased
male fertility) under
elevated daytime temperatures, increased fertility (e.g., increased male
fertility) under
elevated nighttime temperatures and/or increased fertility (e.g., increased
male fertility) under
conditions comprising a large differential between daytime temperatures and
nighttime
temperatures.
Nonnaturally occurring plants of the present invention may comprise any
suitable
insecticidal protein, including, but not limited to Vip3 proteins.
In some embodiments, the nonnaturally occurring plant or plant part comprises
one or
more nucleic acids encoding a Vip3 protein. For example, in some embodiments,
the
nonnaturally occurring plant or plant part comprises the maize MIR162 event,
optionally in a
hemizygous or homozygous state. In embodiments, the nonnaturally occurring
plant or plant
part is an inbred line (e.g., a male inbred line) or a double haploid line. In
embodiments, the
nonnaturally occurring plant or plant part is from an elite maize line. In
embodiments, the
nonnaturally occurring plant or plant part is from a cultivated plant or plant
part. In some
embodiments, the nonnaturally occurring plant or plant part comprises one or
more Vip
nucleotide sequences of as set forth by the Accession Numbers provided in
Table 4.
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Table 4. Examples of Vip3 proteins.
Genital* GenBank
Name Accession No. Accession No. Publication(s)
Vip3Aa1 L48811 AAC37036 International Patent Pub. No. W02013015993
Vip3Aa2 L48812 AAC37037 International Patent Pub. No. W02013015993
Vip3Aa3 U.S. Patent No. 6,137,033; International Patent
Pub. No. W02013015993
Vip3Aa4 AAR81079 U.S. Patent No. 6,656,908; International
Patent Pub. No. W02013015993
Vip3Aa5 AAR81080 U.S. Patent No. 61,56,908; International
Patent Pub. No. W02013015993
Vip3Aa6 AAR/31081 U.S. Patent No. 6,656,908; International
Patent Pub. No. W02013015993
Vip3Aa7 AY044227 AAK95326 International Patent Pub. No.
W02013015993
Vip3Aa8 AF399667 AA3C97481 International Patent Pub. No.
W02013015993
Vip3Aa9 Y17158 CAA76665 International Patent Pub. No. W02013015993
Vip3Aa10 AF373030 AAN60738 International Patent Pub. No.
W02313315993
Vip3Aa1 1 AY489126 AA1t36859 International Patent Pith. No.
W02013015993
Vip3Aa12 AF500478 AA5422456 International Patent Pub. No.
W02013015993
= Vip3Aa13 AY074706 AAL69542 International Patent Pith.
No. W02013015993
Vip3Aa14 M548629 AAQ12340 International Patent Pub. No. W02013015993
Vip3Aa15 AY295778 AAP51131 International Patent Pub. No.
W02013315993
Vip3Aa16 AY739665 AAW65132 International Patent Pub. No.
W02513015993
Vip3Aa17 U.S. Patent No. 6,603,063
Vip3Aal 8 AY945939 AAX49395 International Patent Pub. No.
W02013015993
Vip3Aa19 DQ241674 ABB72459 Inteniatidnal Patent Pub. No.
W02513015993
Vip3Aa19 DQ539887 ABG20428 International Patent PA,. No.
W02013015993
Vip3A220 085539888 AB020429 International Patent PO. No.
W02013015993
Vip3Aa21 0Q426899 ABD84410 International Patent Pub. No.
W02013015993
Vip3Aa22 DQ016968 AAY41427 International Patent Pub. No.
W02013015993
Vip3Aa23 DQ016969 AAY41428 International Patent Pub. No.
W02013015993
Vip3Aa24 EF432794 AB020895 International Patent Pub. No.
W02013015993
Vip3Aa25 EF608501 ABR22260 International Patent Pub. No.
W02013015993
Vip3Aa26 EU294496 ABX90027 International Patent Pub. No.
W02013015993
Vip3Aa27 EU332167 ABY51679 International Patent Pub. No.
W02013015993
Vip3Aa28 0494817 ACR15110 International Patent Pub. No. W02013015993
Vip3Aa29 F1626674 ACV04598 International Patent Pub. No.
W02013015993
Vip3Aa30 F3626675 ACV04599 International Patent Pub. No.
W02013015993
Vip3Aa31 FJ626676 ACV04600 International Patent Pub. No.
W02013015993
Vip3Aa32 0626677 ACV04601 International Patent Pub. No. W02013015993
Vip3Aa33 G13073128 ACY38212 International Patent Pub. No,
W02013015993
Vip3Aa34 GU073129 ACY38213 International Patent Pub. No.
W02013015993
Vip3Aa35 G13733921 ADE06071 International Patent Pub. No.
W02013015993
Vip3Aa36 013951510 ADF43023 International Patent Pub. No.
W02013015993
Vip3Aa37 1Th/1132041 AD318213 International Patent Pub. No.
W02013015993
Vip3Aa38 HM117632 10131411 International Patent Pub. No.
W02013015993
Vip3Aa39 HM117631 AEH31410 International Patent Pub. No.
W02013015993
Vip3Aa40 II54132042 AD318214 International Patent Pub. No.
W02013015993
Vip3Aa41 IIM132043 ADJ18215 International Patent Pub. No.
W02013015993
Vip3Aa42 HQ587048 ADQ73634 International Patent Pith. No.
W02013015993
Vip3Aa43 11(5594534 ADY76643 International Patent Pub. No.
W02313015993
Vip3Aa44 11Q650163 ADW66453 International Patent Pub. No.
W02313015993
Vip3Ab1 AAR40284 U.S. Patent No. 6,603,063; International
Patent Publ. No. W02013015993
Vip3Ab2 DQ054848 AAY88247 International Patent Publication No.
W02013015993
Vip3Ac1 International Patent Pub. No. W02013015993
Vip3Adl U.S. Patent Pub. Na. 2004/0128716; International
Patent Pub. No. W02013015993
Vip3ArI2 A1872071 CA143276 International Patent Pub. No.
W02013015993
Vip3Ae 1 A.1872072 CA143277 International Patent Pub. No.
W02013015993
Vip3Afl A3872070 CA143275 International Patent Pub. No.
W02013015993
Vip3Af2 ADN08753 International Patent Pub. No. W02013015993
Vip3Af3 Inv1117634 AEH31413 International Patent Pub. No.
W02013015993
Vip3Af4 International Patent Pub. No. VV02013015993
Vip3Af5 International Patent Pub. No. W02013015993
Vip3Agl ADN08758 International Patent Pub. No. W02013015993
Vip3Ag2 F3556803 ACL97352 International Patent Pith. No.
W02013015993
Vip3Ag3 1114117633 AEII31412 International Patent Pub. No.
W02013015993
Vip3Ag4 11Q414237 ADZ46177 International Patent Pub. No.
W02013015993
Vip3Ag5 1813542193 A13Y76642 International Patent Pub. No.
W02013015993
Vip3Ahl D13832323 ABH10614 International Patent Pub. No.
W02013015993
Vip35al AY823271 AAV70653
Vip3Bb 1 A03N08760
Vip3Bb2 EF439819 AB030520
Vip3B-like 1034016910 ADI48120
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In some embodiments, the nonnaturally occurring plant or plant part comprises
at
least one nucleotide sequence that is at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to one or more of the Vip nucleotide
sequences of as set
forth by the accession numbers provided in Table 4.
In some embodiments, the normatttrally occurring plant or plant part comprises
at
least one nucleotide sequence that specifically hybridizes to the nucleotide
sequence of one or
more of Vip nucleotide sequences of as set forth by the accession numbers
provided in Table
4 under stringent hybridization conditions.
In some embodiments, the nonnaturally occurring plant or plant part comprises
at
least one nucleotide sequence that encodes the amino acid sequence set forth
in one or more
of Vip nucleotide sequences of as set forth by the accession numbers provided
in Table 4.
In some embodiments, the nonnaturally occurring plant or plant part comprises
at
least one nucleotide sequence that encodes an amino acid sequence that is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to the amino
acid
sequence set forth in one or more of Vip nucleotide sequences of as set forth
by the accession
numbers provided in Table 4.
The present invention also provides nonnaturally occurring nucleic acids. As
used
herein with respect to nucleic acids, the term "nonnaturally occurring" refers
to nucleic acids
that do not naturally exist in nature. In some embodiments, a nonnaturally
occurring nucleic
acid does not naturally exist in nature because it is not in the genetic
background of the
cell/organism in which it naturally resides. That is, the nonnaturally
occurring nucleic acid is
substantially modified by deliberate human intervention from its native form
in composition
(e.g., comprised in a heterologous/recombinant expression cassette with one or
more
heterologous promoter sequences, intron sequences and/or termination
sequences) and/or is
located at a non-native genomic locus. Thus, nonnaturally occurring plants,
and plant parts
of the present invention may comprise one more exogenous or heterologous
nucleotide
sequences and/or one or more nonnaturally occurring copies of a naturally
occurring
nucleotide sequence (i.e., extraneous copies of a gene that naturally occurs
in that species). In
some embodiments, the nonnaturally occurring nucleic acid molecules of the
invention may
comprise any suitable variation(s) from their closest naturally occurring
counterparts. For
example, nonnaturally occurring nucleic acid molecules of the present
invention may
comprise an otherwise naturally occurring nucleotide sequence having one or
more point
mutations, insertions or deletions relative to the naturally occurring
nucleotide sequence.
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Nonnaturally occurring nucleic acids of the present invention may comprise any
suitable marker/allele of interest, including, but not limited to, those
described herein.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more of the chromosomal segments
described in Table 1.
For example, the nonnaturally occurring nucleic acid may comprise, consist
essentially of or
consist of one or more of chromosomal segments 46 to 12473 (e.g., within
chromosomal
segment 7514).
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more nucleic acid sequences derived from
NP2222 maize
germplasm. For example, the nonnaturally occurring nucleic acid may comprise,
consist
essentially of or consist of one or more of the chromosomal segments described
in Table 1,
wherein the chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to the corresponding segment(s) of NP2222
maize
gcrmplasm. In some such embodiments, the nonnaturally occurring nucleic acid
comprises,
consists essentially of or consists of one or more of chromosomal segments 3
to 12768, (e.g.,
chromosomal segments 3, 13, 25, 506, 7514, 7546, 12747, 12753, 12760-12761
and/or
12767-12768) of NP2222 maize germplasm, the reverse complement thereof, an
informative
fragment thereof, or an informative fragment of the reverse complement
thereof.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more nucleic acid sequences derived from
NP2660 maize
germplasm. For example, the nonnaturally occurring nucleic acid may comprise,
consist
essentially of or consist of one or more of the chromosomal segments described
in Table 1,
wherein the chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to the corresponding segment(s) of NP2660
maize
germplasm. In some such embodiments, the nonnaturally occurring nucleic acid
comprises,
consists essentially of or consists of one or more of chromosomal segments 3
to 12743 and/or
one or more of chromosomal segments 12757 to 12768, (e.g., chromosomal
segments 3, 13,
25, 506, 7514, 7546, 12747, 12753, 12760-12761 and/or 12767-12768) of NP2660
maize
germplasm, the reverse complement thereof, an informative fragment thereof, or
an
informative fragment of the reverse complement thereof.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more nucleic acid sequences derived from
NP2276 maize
germplasm. For example, the nonnaturally occurring nucleic acid may comprise,
consist
essentially of or consist of one or more of the chromosomal segments described
in Table 1,
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wherein the chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to the corresponding segment(s) of NP2276
maize
germplasm. In some such embodiments, the nonnaturally occurring nucleic acid
comprises,
consists essentially of or consists of chromosomal segment 1, one or more of
chromosomal
segments 46 to 12743 and/or one or more of chromosomal segments 12757 to
12768, (e.g.,
chromosomal segments 13, 506, 7514, 7546 and/or 12760-12761) of NP2276 maize
germplasm, the reverse complement thereof, an informative fragment thereof, or
an
informative fragment of the reverse complement thereof.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more nucleic acid sequences derived from
ID3461 maize
germplasm. For example, the nonnaturally occurring nucleic acid may comprise,
consist
essentially of or consist of one or more of the chromosomal segments described
in Table 1,
wherein the chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%,
96%, 97%,
98%, 99%, 99.5% or more identical to the corresponding segment(s) of ID3461
maize
germplasm. In some such embodiments, the nonnaturally occurring nucleic acid
comprises,
consists essentially of or consists of one or more of chromosomal segments 1
to 17 (e.g.,
chromosomal segments 1 and/or 13) of ID3461 maize germplasm, the reverse
complement
thereof, an informative fragment thereof, or an informative fragment of the
reverse
complement thereof.
In embodiments, the nonnaturally occurring nucleic acid comprises, consists
essentially of or consists of one or more nucleic acid sequences derived from
a line in Table
11.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of one or more nucleotide sequences that is at
least about 75%, 80%,
85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more of
the
nucleotide sequences set forth in SEQ ID NOs: 1 to 350 and Vip polypeptides
(as described
in Tables 3 and 4), the reverse complement thereof, an informative fragment
thereof, or an
informative fragment of the reverse complement thereof.
In some embodiments, the nonnaturally occurring nucleic acid comprises,
consists
essentially of or consists of at least one nucleotide sequence that encodes an
amino acid
sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,
99.5% or
more identical to the amino acid sequence set forth in one or more of SEQ ID
NOs: 351 to
525 (as described in Table 3).
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In some embodiments, the nonnaturally occurring nucleic acid comprises one or
more
of the desired alleles described in Table 2. For example, in some embodiments,
the isolated
nucleic acid sequence comprises 2, 3,4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15,
20,25, 30, 35, 40,
45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140 or more of
the desired
alleles described in Table 2.
In embodiments, the nonnaturally occurring nucleic acid comprises one or more
of the
desired alleles described in Table 8. For example, in some embodiments, the
nonnaturally
occurring nucleic acid comprises at least about 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12,13, 14, 15,16,
17 or more, or all 18 of the desired alleles described in Table 8.
In embodiments, the nonnaturally occurring nucleic acid comprises one or more
of the
desired alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3,5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In embodiments, the nonnaturally occurring nucleic acid comprises one or more
of the
desired alleles described in Table 10. For example, in some embodiments, the
nonnaturally
occurring nucleic acid comprises 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 20, 25 or more of
the desired alleles described in Table 10.
In some embodiments, the nonnaturally occurring nucleic acid comprises codons
specific for expression in plants.
In some embodiments, the nonnaturally occurring nucleic acid is an isolated
nucleic
acid.
In some embodiments, the nonnaturally occurring nucleic acid comprises one or
more
detectable moieties, such as digoxigenin, fluorescein, acridine-ester, biotin,
alkaline
phosphatase, horseradish permddase,13-glucuronidase, ii-galactosidase,
luciferase, ferritin or
a radioactive isotope. See, e.g., Prober et al. SCIENCE 238:336-340(1987);
European Patent
Nos. 144914 and 119448; and U.S. Patent Nos. 4,582,789 and 4,563,417.
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Nonnaturally occurring nucleic acids of the present invention may comprise any
suitable transgene(s), including, but not limited to, transgenes that encode
gene products that
provide herbicide-resistance, pest-resistance (e.g., a vip3 transgene) and/or
disease-resistance.
In some embodiments, the nonnaturally occurring nucleic acid comprises one or
more
transgenes encoding a gene product that provides resistance to one or more
herbicides. For
example, the nonnaturally occurring nucleic acid may comprise a transgene that
encodes a
gene product that provides glyphosate-, sulfonylurea-, imidazolinione-,
dicamba-, glufisinate-
, phenoxy proprionic acid-, cycloshexome-, traizine-, benzonitrile-, and/or
broxynil-
resistance.
In some embodiments, the nonnaturally occurring nucleic acid comprises one or
more
transgenes encoding a gene product that provides resistance to one or more
pests. For
example, the nonnaturally occurring nucleic acid may comprise a transgene that
encodes a
gene product that provides bacterial-, fungal, gastropod-, insect-, nematode-,
oomycete-,
phytoplasma-, protozoa-, and/or viral-resistance.
In some embodiments, the nonnaturally occurring nucleic acid comprises one or
more
transgenes encoding a gene product that provides resistance to one or more
diseases.
Nonnaturally occurring nucleic acids of the present invention may comprise any
suitable number of nucleic acids. In some embodiments, the nonnaturally
occurring nucleic
acid is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29,
30, 35, 40, 45, 50, 55, 60, 65, 70,75, 80, 85, 90, 95, 100, 125, 150, 175,
200, 225, 250, 275,
300, 325, 350, 375, 400, 450, 500 or more nucleotides in length. In some
embodiments, the
nonnaturally occurring nucleic acid is less than about 5,6, 7, 8,9, 10, 11,
12, 13, 14, 15, 16,
17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40,45, 50, 55, 60,
65, 70, 75, 80, 85,
90, 95, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400,450 or
500
nucleotides in length_ In some embodiments, the nonnaturally occurring nucleic
acid is about
5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, 27, 28, 29, 30,
35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 125, 150, 175, 200,
225, 250, 275, 300,
325, 350, 375, 400, 450 or 500 nucleotides in length.
The present invention also provides expression cassettes comprising one or
more
nonnaturally occurring nucleic acids of the present invention. In some
embodiments, the
expression cassette comprises a nucleic acid encoding a polypeptide that
confers at least one
property (e.g., resistance to a selection agent) that can be used to detect,
identify or select
transformed plant cells and tissues.
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The present invention also provides vectors comprising one or more
nonnaturally
occurring nucleic acids and/or expression cassettes of the present invention.
The present invention also extends to compositions comprising nonnaturally
occurring nucleic acids, expression cassettes and/or vectors of the present
invention.
The present invention extends to uses of nonnaturally occurring nucleic acids,
expression cassettes and vectors of the present invention, including, but not
limited to,
methods of identifying, selecting and/or producing fertile maize plants;
predicting whether
and/or to what extent a maize plant will be fertile; reducing the costs
associated with breeding
and/or seed production programs; and/or to increasing the efficiency of
breeding and/or seed
production programs.
The present invention also provides primers for amplifying nucleic acid
sequences
comprising one or more markers associated with increased fertility (e.g., one
or more markers
of the present invention).
Pruners of the present invention may comprise any nucleic acid sequence useful
for
amplifying one or more markers associated with increased fertility (e.g., one
or more markers
of the present invention).
In some embodiments, the primer comprises nucleic acid sequences useful for
amplifying one or more of the chromosomal segments described in Table 1. For
example, in
some embodiments, the primer pair comprises nucleotide sequences useful for
amplifying
.. one or more of chromosomal segments 46 to 12473 (e.g., chromosomal segment
7514).
The present invention extends to compositions comprising primers of the
present
invention. In some embodiments, the composition comprises a pair of primers,
wherein each
of the primers is a primer of the present invention.
The present invention also provides amplification products comprising one or
more
markers/alleles associated with increased fertility (e.g., one or more
markers/alleles
associated with increased male fertility).
Amplification products of the present invention may be derived from any
suitable
chromosomal segment(s).
In some embodiments, the amplification product is derived from one or more of
the
chromosomal segments described in Table 1. For example, in some embodiments,
the
amplification product is derived from one or more of chromosomal segments 46
to 12473
(e.g., chromosomal segment 7514).
Amplification products of the present invention may comprise any suitable
allele(s) of
interest.
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In some embodiments, the amplification product comprises, consists essentially
of or
consists of one or more nucleic acid sequences derived from NP2222 maize
germplasm. For
example, the amplification product may comprise, consist essentially of or
consist of one or
more of the chromosomal segments described in Table 1 (e.g., chromosomal
segments 3, 13,
25, 506, 7514, 7546, 12747, 12753, 12760-12761 and/or 12767-12768), wherein
the
chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,
99%,
99.5% or more identical to the corresponding segment(s) of NP2222 maize
germplasm.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of one or more nucleic acid sequences derived from NP2660 maize
germplasm. For
example, the amplification product may comprise, consist essentially of or
consist of one or
more of the chromosomal segments described in Table 1 (e.g., chromosomal
segments 3, 13,
25, 506, 7514, 7546, 12747, 12753, 12760-12761 and/or 12767-12768), wherein
the
chromosomal segment is at least about 75%, 80%, 85%, 90%, 95%, 96%, 9701 ,
98%, 99%,
99.5% or more identical to the corresponding segment(s) of NP2660 mai7P
germplasm.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of one or more nucleic acid sequences derived front NP2276 maize
germplasm. For
example, the amplification product may comprise, consist essentially of or
consist of one or
more of the chromosomal segments described in Table 1 (e.g., chromosomal
segments 1, 182,
184, 10230, 10259 and/or 10276-10277), wherein the chromosomal segment is at
least about
75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to the
corresponding segment(s) of NP2276 maize germplasm.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of one or more nucleic acid sequences derived from ID3461 maize
germplasm. For
example, the amplification product may comprise, consist essentially of or
consist of one or
more of chromosomal segments 1 to 17 described in Table 1 (e.g., chromosomal
segments 1
and/or 13), wherein the chromosomal segment is at least about 75%, 80%, 85%,
90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to the corresponding segment(s) of
ID3461
maize germplasm.
In embodiments, the amplification product comprises, consists essentially of
or
consists of one or more nucleic acid sequences derived from a line in Table
11.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence of SEQ ID NOs: 1 to 350, the
reverse
complement thereof, an informative fragment thereof, or an informative
fragment of the
reverse complement thereof.
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In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence that is at least about 75%, 80%,
85%, 90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 1 to
350, the
reverse complement thereof, an informative fragment thereof or an informative
fragment of
the reverse complement thereof.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence that specifically hybridizes to
the nucleotide
sequence of one or more of SEQ ID NOs: 1 to 350, the reverse complement
thereof, an
informative fragment thereof or an informative fragment of the reverse
complement thereof
under stringent hybridization conditions.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence that encodes the amino acid
sequence set forth in
one or more of SEQ ID NOs: 351 to 525 (as described in Table 3).
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence that encodes an amino acid
sequence that is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the amino acid sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as
described in
Table 3).
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one of SEQ NOs: 526 to 613 (as described in Table 9), the
reverse
complement thereof, an informative fragment thereof or an informative fragment
of the
reverse complement thereof.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of at least one nucleotide sequence that is at least about 75%, 80%,
85%, 90%, 95%,
96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ ID NOs: 526
to 613
(as described in Table 9), the reverse complement thereof, an informative
fragment thereof or
an informative fragment of the reverse complement thereof.
In some embodiments, amplification product comprises, consists essentially of
or
consists of at least one nucleotide sequence that specifically hybrirlizPs to
the nucleotide
sequence of one or more of SEQ ID NOs: 526 to 613 (as described in Table 9),
the reverse
complement thereof, an informative fragment thereof or an informative fragment
of the
reverse complement thereof under stringent hybridization conditions.
In some embodiments, the amplification product comprises, consists essentially
of or
consists of one or more of the desired alleles described in Table 2 or the
reverse complement
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thereof. For example, in some embodiments, the amplification product
comprises, consists
essentially of or consists of at least about 2, 3, 4, 5, 6, 7, 8,9, 10, 11,
12, 13, 14, 15, 20,25,
30,35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140
or more of the
desired alleles described in Table 2.
In embodiments, the amplification product comprises one or more of the desired
alleles described in Table 8. For example, in some embodiments, the
amplification product
comprises at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,
17 or more, or all 18
of the desired alleles described in Table 8.
In embodiments, the amplification product comprises one or more of the desired
alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3,5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In some embodiments, the amplification product comprises one or more of the
desired
alleles described in Table 10. For example, in some embodiments, the
amplification product
comprises at least about 2, 3,4, 5, 6,7, 8,9, 10, 11, 12, 13, 14, 15, 20,25 or
more of the
desired alleles described in Table 10.
In some embodiments, the amplification product comprises one or more
detectable
moieties, such as digodgenin, fluorescein, acridine-ester, biotin, alkaline
phosphatase,
horseradish peroxidase, 0-glucuronidase, 0-galactosidase, luciferase, ferritin
or a radioactive
isotope. See, e.g., Prober et at. SCIENCE 238:336-340 (1987); European Patent
Nos. 144914
and 119448; and U.S. Patent Nos. 4,582,789 and 4,563,417.
Amplification products of the present invention may be derived using any
suitable
primers.
Amplification products of the present invention may be generated using any
suitable
technique(s), including, but not limited to, polymerase chain reaction (PCR)
(e.g., Mullis et
al. COLD SPRING HARBOR SYMP. QUANT. BIOL. 51:263-273 (1986); European Patent
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Nos.50,424; 84,796; 258,017; 237,362 and 201,184; U.S. Patent Nos. 4,683,202;
4,582,788
and 4,683,194).
The present invention also provides isolated and purified marker probes (as
described
in Table 9).
Marker probes (as described in Table 9) of the present invention may be
directed
against any suitable allele(s), haplotype(s) and/or molecule(s) of interest.
In some embodiments, the marker probe is directed against a chromosomal
segment
of NP2222 maize germplasm. For example, the marker probe may be directed
against one or
more of chromosomal segments 3 to 12768 as described in. Table 1, (e.g.,
chromosomal
segments 3, 13, 25, 506, 7514, 7546, 12747, 12753, 12760-12761 and/or 12767-
12768) of
NP2222 maize germplasm, the reverse complement thereof, an informative
fragment thereof
or an informative fragment of the reverse complement thereof.
In some embodiments, the marker probe is directed against a chmmosomal segment
of NP2660 maize germplasm. For example, the marker probe may be directed
against one or
more of chromosomal segments 3 to 12743 and/or one or more of chromosomal
segments
12757 to 12768, (as described in Table 1; e.g., chromosomal segments 3, 13,
25, 506, 7514,
7546, 12747, 12753, 12760-12761 and/or 12767-12768) of NP2660 maize germplasm,
the
reverse complement thereof, an informative fragment thereof or an informative
fragment of
the reverse complement thereof.
In some embodiments, the marker probe is directed against a chromosomal
segment
of NP2276 maize germplasm. For example, the marker probe may be directed
against
chromosomal segment 1 as described in Table 1, one or more of chromosomal
segments 46 to
12743 and/or one or more of chromosomal segments 12757 to 12768, (e.g.,
chromosomal
segments 13, 506, 7514, 7546 and/or 12760-12761) of NP2276 maize germplasm,
the
reverse complement thereof, an informative fragment thereof or an informative
fragment of
the reverse complement thereof. In some embodiments, the marker probe is
directed against a
chromosomal segment of ID3461 maize germplasm. For example, the marker probe
may be
directed against one or more of chromosomal segments 1 to 17 of Table 1 (e.g.,
chromosomal
segments 1 and/or 13) of ID3461 maize germplasm, the reverse complement
thereof, an
informative fragment thereof or an informative fragment of the reverse
complement thereof.
In embodiments, the marker probe is directed against a chromosomal segment of
a
line in Table 11, for example, the marker probe may be directed against one or
more of the
chromosomal segments described in Table 1, the reverse complement thereof, an
informative
fragment thereof or an informative fragment of the reverse complement thereof.
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In some embodiments, the marker probe is directed against a nucleotide
sequence that
is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical
to one or more of the nucleotide sequences set forth in SEQ ID NOs: 1 to 350
as described in
Table 3 and in the VIP accession numbers described in Table 4, the reverse
complement
thereof, or an informative fragment thereof.
In some embodiments, the marker probe is directed against one or more
nucleotide
sequences that encode an amino acid sequence that is at least about 75%, 80%,
85%, 90%,
95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more of the amino
acid
sequences set forth in SEQ ID NOs: 351 to 525 (as described in Table 3), the
reverse
complement thereof, or an informative fragment thereof.
In some embodiments, the marker probe is directed against a nucleotide
sequence that
comprises one or more of the desired alleles described in Table 2. For
example, in some
embodiments, the marker probe is directed against a nucleotide sequence that
comprises 2,3,
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,
65, 70, 75, 80, 85, 90,
95, 100, 110, 120, 130, 140 or more of the desired alleles described in Table
2.
In embodiments, the marker probe is directed against a nucleotide sequence
that
comprises one or more of the desired alleles described in Table 8. For
example, in some
embodiments, the marker probe is directed against a nucleotide sequence that
comprises at
least about 2, 3,4, 5, 6,7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17 or more, or
all 18 of the desired
alleles described in Table 8 (see, e.g., the exemplary probes described in
Table 9).
In embodiments, the marker probe is directed against a nucleotide sequence
that
comprises one or more of the desired alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3,5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In some embodiments, the marker probe is directed against a nucleotide
sequence that
comprises one or more of the desired alleles described in Table 10. For
example, in some
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embodiments, the marker probe is directed against a nucleotide sequence that
comprises 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25 or more of the desired
alleles described in Table
10.
In some embodiments, the marker probe is directed against an amino acid
sequence
that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or
more
identical to one or more of the amino acid sequences set forth in SEQ ID NOs:
351 to 525 (as
described in Table 3) or an informative fragment thereof.
In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to a chromosomal segment of NP2222, the reverse
complement thereof, an informative fragment thereof or an informative fragment
of the
reverse complement thereof. In some such embodiments, the chromosomal segment
comprises, consists essentially of or consists of one or more of chromosomal
segments 3 to
12768, as described in Table 1 (e.g., chromosomal segments 3, 13, 25, 506,
7514, 7546,
12747, 12753, 12760-12761 and/or 12767-12768).
In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to a chromosomal segment of NP2660, the reverse
complement thereof, an informative fragment thereof or an informative fragment
of the
reverse complement thereof. In some such embodiments, the chromosomal segment
comprises, consists essentially of or consists of one or more of chromosomal
segments 3 to
12743 and/or one or more of chromosomal segments 12757 to 12768, as described
in Table 1
(e.g., chromosomal segments 3, 13, 25, 506, 7514, 7546, 12747, 12753, 12760-
12761 and/or
12767-12768).
In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to a chromosomal segment of NP2276, the reverse
complement thereof, an informative fragment thereof or an infomuttive fragment
of the
reverse complement thereof. In some such embodiments, the chromosomal segment
comprises, consists essentially of or consists of chromosomal segment 1, one
or more of
chromosomal segments 46 to 12743 and/or one or more of chromosomal segments
12757 to
12768, as described in Table 1 (e.g., chromosomal segments 13, 506, 7514, 7546
and/or
12760-12761
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In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to a chromosomal segment of ID3461, the reverse
complement
thereof, an informative fragment thereof or an informative fragment of the
reverse
complement thereof. In some such embodiments, the chromosomal segment
comprises,
consists essentially of or consists of one or more of chromosomal segments 1
to 17 as
described in Table 1 (e.g., chromosomal segments 1 and/or 13).
For example, the marker probe may be directed against one or more of
chromosomal
segments Ito 17 as described in Table 1 (e.g., chromosomal segments I and/or
13) of
ID3461 maize germplasmõ the reverse complement thereof, an informative
fragment thereof
or an informative fragment of the reverse complement thereof.
In embodiments, the marker probe is directed against one or more chromosomal
segments of a line in Table 11.
In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to one or more of SEQ ID NOs: 1 to 350, the
reverse
complement thereof, an informative fragment thereof or an informative fragment
of the
reverse complement thereof
In some embodiments, the marker probe comprises, consists essentially of or
consists
of a nucleotide sequence that encodes an amino acid sequence that is at least
about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to the amino
acid
sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as described in
Table 3).
In some embodiments, the marker probe comprises, consists essentially of or
consists
of an amino acid sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%,
97%, 98%,
99%, 99.5% or more identical to one or more of SEQ ID NOs: 526 to 613 (as
described in
Table 9), the reverse complement thereof, an informative fragment thereof or
an informative
fragment of the reverse complement thereof.
In some embodiments, the marker probe comprises one or more detectable
moieties,
such as digmdgenin, fluorescein, acridine-ester, biotin, alkaline phosphatase,
horseradish
peroxidase,13-glucuronidase, 0-galactosidase, luciferase, ferritin or a
radioactive isotope. See,
e.g., Prober et al. SCIENCE 238:336-340 (1987); European Patent Nos. 144914
and 119448;
and U.S. Patent Nos. 4,582,789 and 4,563,417.
The present invention also provides methods of identifying, selecting and/or
producing maize plants and plant parts having increased fertility or one or
more
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characteristics associated with increased fertility (e.g., one or more
characteristics associated
with increased male fertility); methods of predicting fertility (e.g., male
fertility) in maize
plants and plant parts; breeding methods; methods of reducing the costs
associated with a
breeding and/or seed production program; and methods of improving seed or
pollen
production in a maize plant (e.g., increasing pollen count per anther, tassel
and/or plant).
The methods of the invention can be practiced using one or more of any of the
markers, alleles, haplotypes, molecules of interest and/or nonnaturally
occurring nucleic acids
described herein.
Methods of identifying maize plants and plant parts having increased fertility
or one
or more characteristics associated with increased fertility may comprise,
consist essentially of
or consist of detecting one or more markers associated with increased
fertility (e.g., one or
more markers of the present invention as described herein) in a maize plant or
plant part (e.g.,
a maize germplasm or an amplification product from a maize germplasm).
Methods of selecting maize plants and plant parts having increased felinity or
one or
more characteristics associated with increased fertility may comprise, consist
essentially of or
consist of detecting one or more markers associated with increased fertility
(e.g., one or more
markers of the present invention as described herein) in a maize plant or
plant part (e.g., a
maize germplasm or an amplification product from a maize germplasm) and
selecting said
maize plant or plant part based upon the presence of said marker(s).
Methods of predicting fertility (e.g., male fertility) in maize plants and
plant parts may
comprise, consist essentially of or consist of detecting the presence of one
or more markers
associated with increased fertility (e.g., one or more markers of the present
invention) in a
maize plant or plant part (e.g., a maize germplasm or an amplification product
from a maize
germplasm). In some embodiments, the presence of said marker(s) in the genome
of said
maize plant or plant part is associated with an increase of at least about 5%,
10%, 15%, 20%,
25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90%, 95%,
100%,
110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 225%, 250%, 275%,
300% or more in the ratio of functionally fertile plants to infertile plants.
For example, in
some embodiments, the presence of said marker(s) in the genome of a maize
plant or plant
part indicates that said maize plant or plant part will likely exhibit
increased pollen
production, increased pollen production per anther, improved pollen
morphology, increased
anther production, increased anther production per tassel, improved anther
morphology,
increased tassel production, improved tassel morphology, increased silk
production,
improved silk morphology, increased silk production per plant, increased
kernel count,
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improved kernel morphology, increased kernel production per ear, decreased
prevalence of
kernel abortion, increased kernel production per plant, increased kernel
viability, increased
fertility under stress conditions (e.g., drought conditions), increased
fertility under elevated
daytime temperatures and/or increased fertility under elevated nighttime
temperatures as
compared to a control plant (e.g., onc or both of its parents, a near isogenic
line lacking a
Vip3 protein coding sequence, etc.).
In embodiments of the methods described herein, a plant or part thereof (or an
ancestor or progeny plant or part thereof) is phenotyped to confirm the
fertility state (e.g., the
state of male fertility) or the presence of characteristics associated with
fertility.
Breeding methods of the present invention may comprise, consist essentially of
or
consist of:
(a) detecting one or more markers associated with increased fertility (e.g.,
one or more
markers of the present invention) in a maize plant or plant part (e.g., a
maize
germplasm or an amplification product from a maize germplasm) and selecting
said
maize plant or plant part for inclusion in a breeding program based upon the
presence
of said marker(s); and/or
(b) detecting the absence of one or more markers associated with increased
fertility (e.g.,
one or more markers of the present invention) in a maize plant or plant part
(e.g., a
maize germplasm or an amplification product from a maize germplasm) and
excluding said maize plant or plant part from a breeding program based upon
the
absence of said marker(s).
In embodiments of the method of (a), the method further comprises crossing the
maize plant (or an ancestor, progeny or sibling thereof) with a second maize
plant that
optionally lacks the marker to produce a progeny maize plant, which optionally
comprises the
marker. Those skilled in the art will appreciate that in the case of an inbred
line, the term
"crossing the maize plant" or "crossing the selected maize plant" can refer to
an identical or
essentially (e.g., at least 95% genetically identical) parent, sibling or
progeny plant.
Optionally, the method further comprises phenotyping the maize plant or plant
part
(or an ancestor or progeny plant or part thereof) to confirm the fertility
state (e.g., the state of
male fertility) or the presence of characteristics associated with fertility.
Maize plants and plant parts selected for inclusion in the breeding program
may be
used to produce one or more generations of fertile progeny. In some
embodiments, each
generation of progeny plants comprises substantially and/or completely fertile
maize plants
and plant parts.
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The invention also encompasses methods for producing a plant having one or
more
characteristics associated with increased male fertility. in embodiments, the
method
.comprises: selecting from a diverse maize plant population a maize plant
comprising a
marker, allele, haplotype, genomic region, and the like associated with
increased male
fertility as described herein; and crossing the maize plant (or an ancestor,
progeny or sibling
thereof) with itself or a second maize plant to produce a progeny plant
comprising the
marker/allele/haplotype/genomic region, thereby producing a plant having one
or more
characteristics associated with increased male fertility. In embodiments, the
second maize
plant does not comprise the marker/allele/haplotype/genotnic region. In
embodiments, the
marker/allele/haplotype/genomic region is detected in nucleic acid from the
first maize plant
and/or progeny plant (e.g., in an amplification product from a nucleic acid
sample from the=
maize plant and/or progeny). Optionally, the method further comprises
phenotyping the
maize plant or plant part (or an ancestor or progeny plant or part thereof) to
confirm the
fertility state (e.g., the state of male fertility) or the presence of
characteristics associated with
fertility.
In embodiments, methods of increasing seed production or reducing the costs
associated with a breeding and/or seed production program comprise, consisting
essentially
of, or consisting of:
(a) detecting one or more markers associated with increased fertility (e.g.
one or more
markers of the present invention) in a maize plant or plant part (e.g., a
maize
germplasm or an amplification product from a maize germplasm) and selecting
said
maize plant or plant part for inclusion in the breeding and/or seed production
program
based upon the presence of said marker(s); and/or
(b) detecting the absence of one or more markers associated with increased
fertility (e.g.,
one or more markers of the present invention) in a maize plant or plant part
(e.g., a
maize gennplasm or an amplification product from a maize germplasm) and
excluding said maize plant or plant part from the breeding and/or seed
production
program based upon the absence of said marker(s).
Optionally, the method further comprises phenotyping the mai7P plant or plant
part
(or an ancestor or progeny plant or part thereof) to confirm the fertility
state (e.g., the state of
male fertility) or the presence of characteristics associated with fertility.
Maize plants and plant parts selected for inclusion in the breeding and/or
seed
production program may be used to produce one or more generations of fertile
progeny. In
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some embodiments, each generation of progeny plants comprises substantially
and/or
completely fertile maize plants and plant parts.
Methods of producing maize plants and plant parts having increased fertility
or one or
more characteristics associated with increased fertility may comprise, consist
essentially of or
consist of:
(a) detecting one or more markers associated with increased fertility (e.g.,
one or more
markers of the present invention) in a maize plant or plant part (e.g., a
maize
germplasm or an amplification product from a maize germplasm) and producing a
maize plant from said maize plant or plant part;
(b) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant or plant part and producing a maize plant from said
maize
plant or plant part;
(c) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant or plant part, detecting said allele(s) in said maize
plant or
plant part (by detecting said allele(s) or an informative fragment thereof in
an
amplification product from said maize plant or plant part, for example) and
producing
a maize plant from said maize plant or plant part;
(d) introducing a nucleic acid comprising one or more alleles associated with
increased =
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant part or plant part, detecting one or more markers
linked to
said allele(s) in said maize plant part or plant part (by detecting said
marker(s) or an
informative fragment thereof in an amplification product from said maize plant
or
plant part, for example) and producing a maize plant from said maize plant or
plant
part;
(e) introducing a genomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant or plant part and producing a
maize plant
lima said maize plant or plant part;
(f) introducing a genomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant or plant part, detecting said
genomic region
in said maize plant or plant part (by detecting said transgene(s) or an
informative
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fragment thereof in an amplification product from said maize plant or plant
part, for
example) and producing a maize plant from said maize plant or plant part;
and/or
(g) introducing a gcnomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant part or plant part, detecting one
or more
markers linked to said genomic region in said maize plant part or plant part
(by
detecting said marker(s) or an informative fragment thereof in an
amplification
product from said maize plant or plant part, for example) and producing a
maize plant
from said maize plant or plant part.
Optionally, the method further comprises phenotyping the maize plant or plant
part
(or an ancestor or progeny plant or part thereof) to confirm the fertility
state (e.g., the state of
male fertility) or the presence of characteristics associated with fertility.
Methods of improving pollen production in a maize plant (e.g., increasing
pollen
count per anther, tassel and/or plant) may comprise, consist essentially of or
consist of:
(a) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant and, optionally, detecting said allele(s) in said
maize plant
(by detecting said allele(s) or an informative fragment thereof in an
amplification
product from said maize plant, for example).
(b) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant and, optionally, detecting one or more markers linked
to said
allele(s) in said maize plant (by detecting said marker(s) or an informative
fragment
thereof in an amplification product from said maize plant part, for example);
(c) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant part and producing a maize plant from said maize plant
part;
(d) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant or plant part, detecting said allele(s) in said maize
plant or
plant part (by detecting said allele(s) or an informative fragment thereof in
an
amplification product from said maize plant or plant part, for example) and
producing
a maize plant from said maize plant or plant part;
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(e) introducing a nucleic acid comprising one or more alleles associated with
increased
fertility (e.g., one or more alleles associated with increased male fertility)
into the
genome of a maize plant or plant part, detecting one or more markers linked to
said
allele(s) in said maize plant or plant part (by detecting said marker(s) or an
informative fragment thereof in an amplification product from said maize plant
or
plant part, for example) and producing a maize plant from said maize plant or
plant
part;
(f) introducing a genomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant or plant part and producing a
maize plant
from said maize plant or plant part;
(g) introducing a genomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant or plant part, detecting said
genomic region
in said maize plant or plant part (by detecting said transgene(s) or an
informative
fragment thereof in an amplification product from said maize plant or plant
part, for
example) and producing a maize plant from said maize plant or plant part;
and/or
(h) introducing a genomic region comprising one or more transgenes associated
with
increased fertility (e.g., one or more transgenes associated with increased
male
fertility) into the genome of a maize plant part or plant part, detecting one
or more
markers linked to said genomic region in said maize plant part or plant part
(by
detecting said marker(s) or an informative fragment thereof in an
amplification
product from said maize plant or plant part, for example) and producing a
maize plant
from said maize plant or plant part.
Optionally, the method further comprises phenotyping the maize plant or plant
part
(or an ancestor or progeny plant or part thereof) to confirm the fertility
state (e.g., the state of
male fertility) or the presence of characteristics associated with fertility.
The invention further contemplates a method of improving seed production from
a
maize plant, comprising: crossing a first maize plant with a second maize
plant, wherein the
first mai7P plant comprises within its genome a marker associated with
increased male
fertility, and wherein said marker is located within one or more of the
chromosomal intervals
described in Table 1, to produce a progeny maize plant comprising said marker;
and using a
progeny maize plant comprising said marker as a pollenator (male) in a cross
with itself or a
second maize plant that functions as a seed parent (female), thereby improving
seed
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production from the cross as compared with a suitable control cross (e.g., a
selfing or cross
with the progeny plant lacking the marker associated with increased
fertility). In
embodiments, the second maize plant lacks the marker. In exemplary
embodiments, the
method reduces the ratio of pollenator parent to seed parent maize plants
required for seed
production by at least about 25% as compared with a suitable control cross. In
embodiments,
the method increases the number of seeds produced per pollenator parent plant
and/or seed
parent plant by at least about 25%.
Optionally, the method further comprises phenotyping the first maize plant
and/or the
progeny plant (or an ancestor or progeny plant or part thereof) to confirm the
fertility state
(e.g., the state of male fertility) or the presence of characteristics
associated with fertility.
Markers for use with the methods of the invention can include any one or more
suitable markers as described herein.
Markers associated with increased fertility (e.g., male fertility) may be
detected using
any suitable marker probe as described herein.
In some embodiments, the marker is detected using a probe designed to detect
an
allele of interest located within one or more of the chromosomal segments
described in Table
1. For example, in some embodiments, the marker is detected using a probe
designed to
detect an allele of interest located within one or more of chromosomal
segments 46 to 12473
(e.g., within chromosomal segment 7514),
In some embodiments, the marker is detected using a probe designed to detect
two or
more alleles located within one or more of the chromosomal segments described
in Table 1.
For example, in some embodiments, the marker is detected using a probe
designed to detect
two or more alleles located within one or more of chromosomal segments 46 to
12473 (e. g , a
haplotype comprising two or more alleles of interest located within
chromosomal segment
7514).
In some embodiments, the marker is detected using a probe designed to detect
alleles
located in distinct chromosomal segments, wherein each of the distinct
chromosomal
segments comprises one or more of the chromosomal segments described in Table
1. For
example, in some embodiments, the marker is detected using probes designed to
detect:
1) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
1;
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2) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located on chromosome 2;
3) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3);
4) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 18 to 45 (e.g., one or more alleles of interest located within
chromosomal
segment 25);
5) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal segment 12747);
6) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal segment 12753);
7) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
12756;
8) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g, one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12757 to 12762 (e.g., one or more alleles of interest located within
chromosomal segment 12760 and/or chromosomal segment 12761);
9) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
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segments 12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal segment 12768);
10) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514), one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3), one or more alleles of interest located within one or more of
chromosomal segments 18 to 45 (e.g., one or more alleles of interest located
within
chromosomal segment 25) and one or more alleles of interest located within one
or
more of chromosomal segments 12763 to 12768 (e.g., one or more alleles of
interest
located within chromosomal segment 12768);
11) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within chromosomal segment 1;
12) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g, one or more alleles of interest located within chromosomal segment
3) and
one or more alleles of interest located on chromosome 2;
13) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
18 to 45 (e.g., one or more alleles of interest located within chromosomal
segment
25);
14) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal
segment 12747);
15) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal
segment 12753);
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16) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within chromosomal segment 12756;
17) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12757 to 12762 (e.g., one or more alleles of interest located within
chromosomal
segment 12760 and/or chromosomal segment 12761);
18) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal
segment 12768);
19)one or more alleles of interest located on chromosome 2, one or more
alleles of
interest located within one or more of chromosomal segments 3 to 17 (e.g., one
or
more alleles of interest located within chromosomal segment 3), one or more
alleles
of interest located within one or more of chromosomal segments 10266 to 10271
(e.g.,
one or more alleles of interest located within chromosomal segment 10269) and
one
or more alleles of interest located within chromosomal segment 12756.
In some embodiments, the marker is detected using a probe designed to detect
one or
more chromosomal segments derived from NP2222 maize germplasm (e.g., NP2222AC
maize germplasm), wherein said one or more chromosomal segments comprises,
consists
essentially of or consists of one or more of the chromosomal segments
described in Table 1.
For example, in some embodiments, the marker is detected using a probe
designed to detect
one or more of chromosomal segments 3 to 12768, (e.g., chromosomal segments 3,
13, 25,
506, 7514, 7546, 12747, 12753,12760-12761 and/or 12767-12768) derived from
NP2222
maize germplasm.
In some embodiments, the marker is detected using a probe designed to detect
one or
more chromosomal segments derived from NP2660 maize germplasm (e.g., NP2660AC
NIL-
2343, NP2660AC N1L-3338 or NP2660AC NIL-3367 maize germplasm), wherein said
one
or more chromosomal segments comprises, consists essentially of or consists of
one or more
of the chromosomal segments described in Table 1. For example, in some
embodiments, the
marker is detected using a probe designed to detect one or more of chromosomal
segments 3
to 12743 and/or one or more of chromosomal segments 12757 to 12768, (e.g.,
chromosomal
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segments 3, 13, 25, 506, 7514,7546, 12747, 12753, 12760-12761 and/or 12767-
12768)
derived from NP2660 maize gertnplasm.
In some embodiments, the marker is detected using a probe designed to detect
one or
more chromosomal segments derived from NP2276 maize germplasm(e.g., NP2276AC
NIL
maize germplasm), wherein said one or more chromosomal segments comprises,
consists
essentially of or consists of one or more of the chromosomal segments
described in Table 1.
For example, in some embodiments, the marker is detected using a probe
designed to detect
chromosomal segment 1, one or more of chromosomal segments 46 to 12743 and/or
one or
more of chromosomal segments 12757 to 12768, (e.g., chromosomal segments 13,
506, 7514,
7546 and/or 12760-12761) derived from NP2276 maize germplasm.
In some embodiments, the marker is detected using a probe designed to detect
one or
more chromosomal segments derived from ID3461 maize germplasm, wherein said
one or
more chromosomal segments comprises, consists essentially of or consists of
one or more of
the chromosomal segments described in Table 1. For example, in some
embodiments, the
marker is detected using a probe designed to detect one or more of chromosomal
segments 1
to 17 (e.g., chromosomal segments 1 and/or 13) derived from 1D3461 maize
germplasm.
In embodiments, the marker is detected using a probe designed to detect one or
more
chromosomal segments derived from a line in Table 11.
In some embodiments, the marker is detected using a probe designed to detect
at least
one of SEQ ID NOs: 1 to 350 (as described in Table 3).
In some embodiments, the marker is detected using a probe designed to detect
any
nucleotide sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%,
98%, 99%,
99.5% or more identical to one or more of SEQ ID NOs: 1 to 350 (as described
in Table 3).
In some embodiments, the marker is detected using a probe designed to detect
any
nucleotide sequence that specifically hybridizes to the nucleotide sequence of
one or more of
SEQ ID NOs: 1 to 350 (as described in Table 3) under stringent hybridization
conditions. In
some embodiments, the marker is detected using a probe designed to detect any
nucleotide
sequence that encodes the amino acid sequence set forth in one or more of SEQ
ID NOs: 351
to 525 (as described in Table 3).
In some embodiments the marker is detected using a probe designed to detect
any
nucleotide sequence that encodes an amino acid sequence that is at least about
75%, 80%,
85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to the amino acid
sequence
set forth in one or more of SEQ ID NOs: 351 to 525 (as described in Table 3).
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In some embodiments, the marker is detected using a probe designed to detect
at least
one of SEQ lD NOs: 526 to 613 (as described in Table 9).
In some embodiments, the masker is detected using a probe designed to detect
any
nucleotide sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%,
98%, 99%,
99.5% or more identical to one or more of SEQ ID NOs: 526 to 613 (as described
in Table 9).
In some embodiments, the marker is detected using a probe designed to detect
any
nucleotide sequence that specifically hybridizes to the nucleotide sequence of
one or more of
SEQ ID NOs: 526 to 613 (as described in Table 9) under stringent hybridization
conditions.
In some embodiments, the masker is detected using a probe designed to detect
one or
more of the desired alleles described in Table 2. For example, in some
embodiments, the
marker is detected using a probe designed to detect 2, 3, 4, 5, 6, 7, 8,9, 10,
11, 12, 13, 14, 15,
20,25, 30, 35, 40, 45, 50, 55, 60,65, 70, 75, 80, 85, 90, 95, 100, 110, 120,
130, 140 or more
of the desired alleles described in Table 2.
In embodiments, the marker is detected using a probe designed to detect one or
more
of the desired alleles described in Table 8. For example, in some embodiments,
the marker is
detected using a probe designed to detect at least about 2, 3, 4, 5, 6, 7,
8,9, 10, 11, 12, 13, 14,
15, 16, 17 or more, or all 18 of the desired alleles described in Table 8
(see, e.g., the
exemplary probes described in Table 9).
In embodiments, the marker is detected using a probe designed to detect one or
more
of the desired alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3,5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In some embodiments, the marker is detected using a probe designed to detect
one or
more of the desired alleles described in Table 10. For example, in some
embodiments, the
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marker is detected using a probe designed to detect 2, 3,4, 5, 6,7, 8,9, 10,
11, 12, 13, 14, 15,
20,25 or mom of the desired alleles described in Table 10.
In some embodiments, the marker is detected using a probe designed to detect
the
reverse complement of one of a marker as described herein.
In some embodiments, the marker is detected using a probe designed to detect
an
informative fragment of one of the markers as described herein.
In some embodiments, the marker is detected using a probe designed to detect a
marker linked to one or more of the markers described herein. That is, the
marker may be
detected using a probe designed to detect a marker that is in linkage
disequilibrium with any
of the markers described herein.
In some embodiments, the marker is detected using a probe designed to detect a
marker located within about 20 cM, 15 cM, 10 cM, 5 cM or 1 cM or less of any
one of the
markers described herein. For example, in some embodiments, the marker is
detected using a
probe designed to detect one or more markers located within about 5 cM, 1cM or
less of
chromosomal segment 7514.
Markers associated with increased fertility may be detected in any suitable
plant part,
including, but not limited to, amplification products derived from maize
germplasm.
Markers associated with increased fertility may be detected in any suitable
amplification product, for example, an amplificatiOn product as described
herein.
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of one or more of the chromosomal
segments
described in Table 1. For example, in some embodiments, the marker may be
detected in an
amplification product comprising, consisting essentially of, or consisting of:
(a) chromosomal segment 1;
(b) one or more of chromosomal segments 3 to 17 (e.g., within chromosomal
segment 3);
(c) one or more of chromosomal segments 18 to 45 (e.g., within chromosomal
segment
25);
(d) one or more of chromosomal segments 46 to 12473 (e.g, within chromosomal
segment 7514);
(e) one or more of chromosomal segments 12744 to 12749 (e.g., within
chromosomal
segment 12747);
(f) one or more of chromosomal segments 12750 to 12755 (e.g., within
chromosomal
segment 12753);
(g) one or more of chromosomal segment 12756;
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(h) one or more of chromosomal segments 12757 to 12762 (e.g., within
chromosomal
segment 12760 and/or chromosomal segment 12761); or
(i) one or more of chromosomal segments 12763 to 12768 (e.g., within
chromosomal
segment 12768).
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of at least one of SEQ ID NOs: 1 to
350 (as described
in Table 3).
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of a nucleotide sequence that is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more
of
SEQ ID NOs: 1 to 350 (as described in Table 3).
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of a nucleotide sequence that
specifically hybridizes to
the nucleotide sequence of one or more of SEQ ID NOs: 1 to 350 (as described
in Table 3)
under stringent hybridization conditions.
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of a nucleotide sequence that encodes
the amino acid
sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as described in
Table 3).
In some embodiments, the marker is detected in an amplification product
comprising.
consisting essentially of, or consisting of a nucleotide sequence that encodes
an amino acid
sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,
99.5% or
more identical to the amino acid sequence set forth in one or more of SEQ ID
NOs: 351 to
525 (as described in Table 3).
In some embodiments, the marker is detected using a probe designed to detect
at least
one of SEQ ID NOs: 526 to 613 (as described in Table 9).
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of a nucleotide sequence that is at
least about 75%,
80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more
of
SEQ ID NOs: 526 to 613 (as described in Table 9).
In some embodiments, the marker is detected in an amplification product
comprising,
consisting essentially of, or consisting of a nucleotide sequence that
specifically hybridizes to
the nucleotide sequence of one or more of SEQ ID NOs: 526 to 613 (as described
in Table 9)
under stringent hybridization conditions.
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In some embodiments, the marker is detected in an amplification product
comprising
one or more of the desired alleles described in Table 2. For example, in some
embodiments,
the marker is detected in an amplification product comprising 2, 3, 4, 5,6, 7,
8,9, 10, 11, 12,
13, 14, 15, 20, 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,
100, 110, 120, 130,
140 or more of the desired alleles described in Table 2.
In embodiments, the marker is detected in an amplification product comprising
one or
more of the desired alleles described in Table 8. For example, in some
embodiments, the
marker is detected in an amplification product comprising at least about 2, 3,
4, 5, 6, 7, 8,9,
10, 11, 12, 13, 14, 15, 16, 17 or more, or all 18 of the desired alleles
described in Table 8
(see, e.g., the exemplary amplification primers and probes described in Table
9).
In embodiments, the marker is detected in an amplification product comprising
one or
more of the desired alleles:
(a) on chromosomes (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
(t) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In some embodiments, the marker is detected in an amplification product
comprising
one or more of the desired alleles described in Table 10. For example, in some
embodiments,
the marker is detected in an amplification product comprising 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12,
13, 14, 15, 20, 25 or more of the desired alleles described in Table 10.
Alleles may be introduced into maize plants and plant parts using any suitable
method, including, but not limited to, crossing, transfection, transduction,
protoplast
transformation or fusion, double haploid technique, embryo rescue, or by any
other nucleic
acid transfer system. In some embodiments, one or more alleles associated with
increased
fertility is/are introduced into the genome of a maize plant or plant part
through a breeding
program comprising MAS using one or more of the markers described herein.
Thus, in some embodiments, methods of producing maize plants and plant parts
having increased fertility (e.g., increased male fertility) or one or more
characteristics
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associated with increased fertility and/or maize plants and plant parts
comprising one or more
alleles associated with increased fertility and methods of improving pollen
production may
comprise:
(a) crossing a first maize plant or plant part with a second maize plant or
plant part,
wherein the fast maize plant or plant part comprises within its genome one or
more
alleles associated with increased fertility (e.g., one or more alleles
associated with
increased male fertility);
(b) crossing a first maize plant or plant part with a second maize plant or
plant part,
wherein the first maize plant or plant part comprises within its genome one or
more
haplotypes associated with increased fertility (e.g , one or more alleles
associated
with increased male fertility);
(c) detecting the presence of one or more alleles associated with increased
fertility (e.g.,
one or more alleles associated with increased male fertility) in a first maize
plant or
plant part (by detecting said allele(s) or an informative fragment thereof in
an
amplification product from said maize plant or plant part, for example) and
crossing
the first maize plant or plant part with a second maize plant or plant part
lacking
said allele(s);
(d) detecting the presence of one or more haplotypes associated with
increased fertility
(e.g., one or more haplotypes associated with increased male fertility) in a
first
maize plant or plant part (by detecting said haplotype(s) or an informative
fragment
thereof in an amplification product from said maize plant or plant part, for
example)
and crossing the first maize plant or plant part with a second maize plant or
plant
part lacking said allele(s);
(e) detecting the presence of one or more transgenes associated with
increased fertility
(e.g., one or more transgenes associated with increased male fertility) in a
fast
maize plant or plant part (by detecting said transgene(s) or an informative
fragment
thereof in an amplification product from said maize planter plant part, for
example)
and crossing the fast maize plant or plant part with a second maize plant or
plant
part lacking said marker(s);
(f) detecting the presence of a genomic region comprising one or more
transgenes
associated with increased fertility (e.g., one or more transgenes associated
with
increased male fertility) in a first maize plant or plant part (by detecting
said
genomk region or an informative fragment thereof in an amplification product
from
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said maize plant or plant part, for example) and crossing the first maize
plant or
plant part with a second mai 7P plant or plant part lacking said genomic
region;
(g) detecting the presence of one or more markers associated with increased
fertility
(e.g., one or more markers associated with increased male fertility) in a
first maize
plant or plant part (by detecting said marker(s) or an informative fragment
thereof in
an amplification product from said maize plant or plant part, for example) and
crossing the first maize plant or plant part with a second maize plant or
plant part
lacking said marker(s);
(h) crossing a first maize plant or plant part comprising one or more
alleles associated
with increased fertility (e.g., one or more alleles associated with increased
male
fertility) with a second maize plant or plant part that lacks said allele(s)
and
backcrossing for one or more generations progeny comprising said allele(s)
with
said second maize plant or plant part;
(i) detecting the presence of one or more alleles associated with increased
fertility (e.g.,
one or more alleles associated with increased male fertility) in a first maize
plant or
plant part (by detecting said allele(s) or an informative fragment thereof in
an
amplification product from said maize plant or plant part, for example),
crossing the
first maize plant or plant part with a second maize plant or plant part
lacking said
allele(s), and backcrossing for one or more generations progeny comprising
said
allele(s) with said second maize plant or plant part;
(j) detecting the presence of one or more haplotypes associated with
increased fertility
(e.g., one or more haplotypes associated with increased male fertility) in a
first
maize plant or plant part (by detecting said haplotype(s) or an informative
fragment
thereof in an amplification pioduct from said maize plant or plant part, for
example), crossing the first maize plant or plant part with a second maize
plant or
plant part lacking said haplotype(s), and backcrossing for one or more
generations
progeny comprising said haplotype(s) with said second maize plant or plant
part;
(k) detecting the presence of one or more transgenes associated with
increased fertility
(e.g., one or more transgenes associated with increased male fertility) in a
first
maize plant or plant part (by detecting said transgene(s) or an informative
fragment
thereof in an amplification product from said maize plant or plant part, for
example), crossing the first maize plant or plant part with a second maize
plant or
plant part lacking said transgene(s), and backcrossing for one or more
generations
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progeny comprising said transgene(s) with said second maize plant or plant
part;
and/or
(1) detecting the presence of a genomic region comprising one or more
transgenes
associated with increased fertility (e.g., one or more transgenes associated
with
increased male fertility) in a first maize plant or plant part (by detecting
said
genomic region or an informative fragment thereof in an amplification product
from
said maize plant or plant part, for example), crossing the first maize plant
or plant
part with a second maize plant or plant part lacking said genomic region, and
backcrossing for one or more generations progeny comprising said genomic
region
with said second maize plant or plant part; and/or
(m) detecting the presence of one or more markers associated with
increased fertility
(e.g., one or more markers associated with increased male fertility) in a
first maize
plant or plant part (by detecting said marker(s) or an informative fragment
thereof in
an amplification product from said maize plant or plant part, for example),
crossing
the first maize plant or plant part with a second maize plant or plant part
lacking
said marker(s), and backcrossing for one or more generations progeny
comprising
said marker(s) with said second maize plant or plant part.
Optionally, the method further comprises phenotyping the maize plant or plant
part
(or an ancestor or progeny plant or part thereof) to confirm the fertility
state (e.g., the stale of
male fertility) or the presence of characteristics associated with fertility.
Any suitable allele(s) may be introduced into the maize plant or plant part,
including,
but not limited to, any one or more of the alleles described.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more of the chromosomal segments described in Table 1 is
introduced
into the maize plant or plant part. For example, in some embodiments, one or
more of
chromosomal segments 46 to 12473 (e.g., chromosomal segment 7514) is
introduced into the
maize plant Or plant part.
In some embodiments, one or more haplotypes associated with increased
fertility
(e.g., increased male fertility) is introduced into the maize plant or plant
part. The haplotype
can include any of one or more of the haplotypes as described herein. In some
such
embodiments, the haplotype comprises, consists essentially of or consists of
two or more
alleles of interest located within one or more of the chromosomal segments
described in
Table 1 (e.g., a haplotype comprising two or more alleles of interest located
within
chromosomal segment 7514). In some such embodiments, the haplotype comprises,
consists
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essentially of or consists of one or more alleles of interest located within a
first chromosomal
segment and one or more alleles of interest located within a second
chromosomal segment
different from the first chromosomal segment, wherein each of the first and
second
chromosomal segments comprises one or more of the chromosomal segments
described in
Table 1. For example, the haplotype may comprise, consist essentially of or
consist of:
1) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
1;
2) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located on chromosome 2;
3) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3);
4) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 18 to 45 (e.g., one or more alleles of interest located within
chromosomal
segment 25);
5) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal segment 12747);
6) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal segment 12753);
7) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g, one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within chromosomal segment
12756;
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8) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e_g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12757 to 12762 (e.g., one or more alleles of interest located within
chromosomal segment 12760 and/or chromosomal segment 12761);
9) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514) and one or more alleles of interest located within one or more of
chromosomal
segments 12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal segment 12768);
10) one or more alleles of interest located within one or more of chromosomal
segments
46 to 12473 (e.g., one or more alleles of interest located within chromosomal
segment
7514), one or more alleles of interest located within one or more of
chromosomal
segments 3 to 17 (e.g., one or more alleles of interest located within
chromosomal
segment 3), one or more alleles of interest located within one or more of
chromosomal segments 18 to 45 (e.g., one or more alleles of interest located
within
chromosomal segment 25) and one or more alleles of interest located within one
or
more of chromosomal segments 12763 to 12768 (e.g., one or more alleles of
interest
located within chromosomal segment 12768);
11) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within chromosomal segment 1;
12) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located on chromosome 2;
13)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
18 to 45 (e.g., one or more alleles of interest located within chromosomal
segment
25);
14)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
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12744 to 12749 (e.g., one or more alleles of interest located within
chromosomal
segment 12747);
15) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12750 to 12755 (e.g., one or more alleles of interest located within
chromosomal
segment 12753);
16) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within chromosomal segment 12756);
17) one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
1275 7 to 12762 (e.g., one or more alleles of interest located within
chromosomal
segment 12760 and/or chromosomal segment 12761);
18)one or more alleles of interest located within one or more of chromosomal
segments 3
to 17 (e.g., one or more alleles of interest located within chromosomal
segment 3) and
one or more alleles of interest located within one or more of chromosomal
segments
12763 to 12768 (e.g., one or more alleles of interest located within
chromosomal
segment 12768);
19)one or more alleles of interest located on chromosome 2, one or more
alleles of
interest located within one or more of chromosomal segments 3 to 17 (e.g., one
or
snore alleles of interest located within chromosomal segment 3), one or more
alleles
of interest located within one or more of chromosomal segments 10266 to 10271
(e.g.,
one or more alleles of interest located within chromosomal segment 10269) and
one
or more alleles of interest located within chromosomal segment 12756.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more chromosomal segments derived from NP2222 maize
germplasm is
introduced into the maize plant or plant past, wherein said one or more
chromosomal
segments comprises, consists essentially of or consists of one or more of the
chromosomal
segments described in fable 1. For example, in some embodiments, one or more
of
chromosomal segments 310 12768, (e.g., chromosomal segments 3, 13, 25, 506,
7514, 7546,
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12747, 12753, 12760-12761 and/or 12767-12768) derived from NP2222 maize
germplasm is
introduced into the maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more chromosomal segments derived from NP2660 maize
germplasm is
introduced into the maize plant or plant part, wherein said one or more
chromosomal
segments comprises, consists essentially of or consists of one or more of the
chromosomal
segments described in Table 1. For example, in some embodiments, one or more
of
chromosomal segments 3 to 12743 and/or one or more of chromosomal segments
1275710
12768, (e.g., chromosomal segments 3, 13, 25, 506, 7514, 7546, 12747, 12753,
12760-12761
and/or 12767-12768) derived from NP2660 maize germplasm is introduced into the
maize
plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more chromosomal segments derived from NP2276 maize
germplasm is
introduced into the maize plant or plant part, wherein said one or more
chromosomal
segments comprises, consists essentially of or consists of one or more of the
chromosomal
segments described in Table I. For example, in some embodiments, chromosomal
segment
1, one or more of chromosomal segments 46 to 12743 and/or one or more of
chromosomal
segments 12757 to 12768, (e.g, chromosomal segments 13, 506, 7514, 7546 and/or
12760-
12761) derived from N1'2276 maize germplasm is introduced into the maize plant
or plant
part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more chromosomal segments derived from 1133461 maize
germplasm is
introduced into the maize plant or plant part, wherein said one or more
chromosomal
segments comprises, consists essentially of or consists of one or more of the
chromosomal
segments described in Table 1. For example, in some embodiments, one or more
of
chromosomal segments Ito 17 (e.g., chromosomal segments 1 and/or 13) derived
from
I133461 maize germplasm is introduced into the maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more chromosomal segments derived from a maize line in
Table 11 is
introduced into the maize plant or plant part, wherein said one or more
chromosomal
segments comprises, consists essentially of or consists of one or more of the
chromosomal
segments described in Table 1.
In some embodiments, one or more genes associated with increased fertility
(e.g.,
increased male fertility) is introduced into the maize plant or plant part.
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In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of at least one of the nucleotide sequences of SEQ ID NOs: 1 to 350
(as described
in Table 3) is introduced into the maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of at least one nucleotide sequence that is at least about 75%,
80%, 85%, 90%,
95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more of SEQ 1D NOs:
1 to
350 (as described in Table 3) is introduced into the maize plant or plant
part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of at least one nucleotide sequence that specifically hybridizes to
the nucleotide
sequence of one or more of SEQ ID NOs: 1 to 350 (as described in Table 3)
under stringent
hybridization conditions is introduced into the maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of at least one nucleotide sequence that encodes the amino acid
sequence set forth
in one or more of SEQ ID NOs: 351 to 525 (as described in Table 3) is
introduced into the
maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of at least one nucleotide sequence that encodes an amino acid
sequence that is at
least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or more
identical to
the amino acid sequence set forth in one or more of SEQ ID NOs: 351 to 525 (as
described in
Table 3) is introduced into the main plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of one or more of the desired alleles described in Table 2 is
introduced into the
maize plant or plant part.
In embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of
one or more of the desired alleles described in Table 8 is introduced into the
maize plant or
plant part.
In embodiments, a nucleic acid is introduced into a maize plant or plant part,
the
nucleic acid comprising, consisting essentially of, or consisting of one or
more of the desired
alleles:
(a) on chromosome 5 (QTL 5.1 and/or QTL 5.2) as described in Table 8;
(b) on chromosome 3 as described in Table 8;
(c) on chromosome 7 as described in Table 8;
(d) on chromosome 10 as described in Table 8;
(e) on chromosomes 3 and 5 as described in Table 8;
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(f) on chromosomes 5 and 7 as described in Table 8;
(g) on chromosomes 3, 5 and 7 as described in Table 8;
(h) on chromosomes 5 and 10 as described in Table 8;
(i) on chromosomes 3, 5 and 10 as described in Table 8; or
(j) any combination of (a) to (i).
In some embodiments, a nucleic acid comprising one or more of the desired
alleles
described in Table 10 is introduced into the maize plant or plant part.
In some embodiments, a nucleic acid comprising, consisting essentially of, or
consisting of the reverse complement of one of the nucleic acids described
herein is
introduced into the maize plant or plant part.
In some embodiments, the nucleic acid introduced into the maize plant or plant
part is
not in the natural genetic background of the maize plant (e.g., is not
naturally occurring in the
maize line or variety, and has been introduced therein by human intervention).
In the methods of the invention described herein, the marker, allele and/or
haplotype,
and the like, is detected in nucleic acid (e.g., a nucleic acid sample) from
plant or plant part.
In embodiments, the marker, allele and/or haplotype, and the like, is detected
in an
amplification product from a nucleic acid sample from the plant or plant part.
The methods of the invention can be used for forward breeding or for
introgressing
one or more genetic loci associated with increased fertility into a new
genetic background
(e.g., to introgress the trait into an elite inbred maize line).
Methods of the present invention may be used to increase the efficiency of a
breeding
and/or seed production program (e.g., seed production from a double haploid or
inbred line)
by reducing the number of male plants required for breeding and/or seed
production, reducing
the ratio of male to female plants required for breeding and/or seed
production, reducing the
costs associated with breeding and/or seed production (e.g., the cost(s) of
land and seedbed
preparation, planting, fertilizer application, weed control, harvesting and/or
testing),
increasing pollen production (e.g., pollen production per antherhasselplant),
improving
pollen morphology, increasing pollen viability, increasing anther production
(e.g., anther
production per tassel/plant), improving anther morphology, increasing anther
viability,
increasing tassel production (e.g., tassel production per plant), improving
tassel morphology,
increasing tassel viability, increasing silk production (e.g., silk production
per ear/plant),
improving silk morphology, increasing silk viability, increasing seed
production (e.g., seed
production per ear/plant), improving seed morphology, decreasing the
prevalence of kernel
abortion, increasing seed viability, increasing male fertility under stress
conditions (e.g.,
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drought conditions), increasing fertility (e.g., male fertility) under
elevated daytime
temperatures and/or increasing fertility (e.g., male fertility) under elevated
nighttime
temperatures.
In some embodiments, methods of the present invention increase the efficiency
of a
breeding and/or seed production program by at least about 5%, 10%, 15%, 20%,
25%, 30%,
35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90%, 95%, 100%, 110%,
120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 225%, 250%, 275% 300% or
more as compared to a control breeding/seed production program (e.g., a
breeding/seed
production program using the same maize varieties in the absence of marker-
assisted
selection with markers of the present invention).
In some embodiments, methods of the present invention reduce the number of
male
plants required for a breeding and/or seed production program by at least
about 5%, 10%,
15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90%,
95%, 96%, 97%, 98%, 99% or more as compared to a control breeding program
(e.g., a
breeding program using the same maize varieties in the absence of marker-
assisted selection
with markers of the present invention).
In some embodiments, methods of the present invention reduce the ratio of male
to
female plants required for a breeding and/or seed production program by at
least about 5%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%,
90%, 95%, 96%, 97%, 98%, 99% or more as compared to a control breeding program
(e.g., a
breeding program using the same maize varieties in the absence of marker-
assisted selection
with markers of the present invention).
In some embodiments, methods of the present invention reduce one or more of
the
costs associated with a breeding and/or seed production program (e. g. , the
cost(s) of land and
seedbed preparation, planting, fertilizer application, weed control,
harvesting and/or testing)
by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,
65%,
70%, 75% 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more as compared to a
control
breeding/seed production program (e.g., a breeding/seed production program
using the same
maizP varieties in the absence of marker-assisted selection with markers of
the present
invention). In embodiments, the seed production program produces seed from a
double
haploid or inbred line).
In some embodiments, methods of the present invention reduce the overall cost
associated of a breeding and/or seed production program by at least about 5%,
10%, 15%,
20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90%, 95%,
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96%, 97%, 98%, 99% or more as compared to a control breeding/seed production
program
(e.g., a breeding/seed production program using the same maize varieties in
the absence of
marker-assisted selection with markers of the present invention). In
embodiments, the seed
production program produces seed from a double haploid or inbred line).
In some embodiments, methods of the present invention increase the number of
pollen
grains produced per plant in a breeding and/or seed production program by at
least about 5%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%,
90%, 95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%,
225%, 250%, 275%, 300% or more as compared to a control breeding/seed
production
program (e.g., a breeding/seed production program using the same maize
varieties in the
absence of marker-assisted selection with markers of the present invention).
In some embodiments, methods of the present invention increase the number of
anthers produced per plant in a breeding and/or seed production program by at
least about
5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%,
85%, 90%, 95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%,
200%, 225%, 250%, 275%, 300% or more as compared to a control breeding/seed
production
program (e.g., a breeding/seed production program using the same maize
varieties in the
absence of marker-assisted selection with markers of the present invention).
In some embodiments, methods of the present invention increase the number of
tassels produced per plant in a breeding and/or seed production program by at
least about 5%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%,
90%, 95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%,
225%, 250%, 275%, 300% or more as compared to a control breeding/seed
production
program (e.g., a breeding/seed production program using the same maize
varieties in the
absence of marker-assisted selection with markers of the present invention).
In some embodiments, methods of the present invention increase the number of
seeds
produced per plant in a breeding and/or seed production program by at least
about 5%, 10%,
15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%, 90%,
95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 225%,
250%, 275%, 300% or more as compared to a control breeding/seed production
program
(e.g., a breeding/seed production program using the same maize varieties in
the absence of
marker-assisted selection with markers of the present invention).
In some embodiments, methods of the present invention increase the number of
seeds
produced per male plant in a breeding and/or seed production program by at
least about 5%,
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10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%,
90%, 95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%,
225%, 250%, 275%, 300% or more as compared to a control breeding/seed
production
program (e.g., a breeding/seed production program using the same maize
varieties in the
absence of marker-assisted selection with markers of the present invention).
In some embodiments, methods of the present invention increase the number of
seeds
produced per female plant in a breeding and/or seed production program by at
least about 5%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% 80%, 85%,
90%,95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%,200%,
225%, 250%, 275%, 300% or more as compared to a control breeding/seed
production
program (e.g., a breeding/seed production program using the same maize
varieties in the
absence of marker-assisted selection with markers of the present invention).
Methods of the present invention can be practiced with and/or used to
identify, breed,
select and/or produce any suitable maize plant or plant part.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is a member of the Stiff Stalk heterotic group.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is a member of the non-Stiff Stalk heterotic
group.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is a member of the Iodent heterotic group.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is a B14, B37, B73, 0H43 or Iodent maize plant
or plant part. In
embodiments, the donor plant or plant part is from the B14 group. In
embodiments, the
recipient plant or plant part is from the B37 or B73 group.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is an NP2391, NP2460, N1P2222, NP2660, NP2276
or ID3461
maize plant or plant part.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is from a line described in Table 11.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is derived from a B14, B37, B73, 0H43 or lodent
maize plant or
plant part.
=
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In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is derived from an NP2391, NP2460, NP2222,
NP2660, NP2276
or ID3461 maize plant or plant part.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is derived from a line in Table 11.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is of a nonnaturally occurring maize line or
variety. In
representative embodiments, the nonnaturally occurring plant or plant part
(e.g., the donor
and/or the recipient plant or plant part) is from a cultivated plant or plant
part.
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is an inbred maize plant or plant part.
In some embodiments, the maize plant or plant part (e.g. the donor and/or the
recipient plant or plant part) is a double haploid maize plant or plant part.
In some embodiments, an inbred or double haploid or inbred maize plant or
plant part
(e.g., the donor and/or the recipient plant or plant part) is a male inbred or
double haploid
plant or plant part (e.g., is used as a pollenator in a cross or to self).
In some embodiments, the maize plant or plant part (e.g., the donor and/or the
recipient plant or plant part) is of an elite variety of maize. For example,
in some
embodiments, the maize plant or plant part is NP2222, NP2660, NP2276, NP2391
or
NP2460.
In embodiments, the maize plant or plant part (e.g., the recipient plant or
plant part)
has a decrease in male fertility when hemizygous and/or homozygous for a v1p3
gene (for
example, a vip3a gene, as illustrated by maize event MIR162). In embodiments,
the maize
plant or plant part is not functionally fertile or is even male sterile when
hemizygous and/or
homozygous for a vip3 gene.
In some embodiments, the genome of the maize plant or plant part is at least
about
50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or
more identical to an elite variety of maize. For example, in some embodiments,
the genome
of the maize plant or plant part is at least 50%, 55%, 60%, 65%, 70%, 75%,
80%, 85%, 90%,
95%, 96%, 97%, 98%, 99%, 99.5% or more identical to that of NP2222, NP2660,
NP2276,
N1'2391 and/or NP2460.
In some embodiments, the maize plant or plant part is the progeny of a cross
between
an elite variety of maize and a variety of maize that comprises an allele
associated with
increased fertility. For example, in some embodiments, the genome of the elite
variety of
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maize is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%,
99%
or 100% identical to that of NP2222, NP2660, NP2276, NP2391 and/or NP2460 or
an elite
line described in Table 11; and the genome of the variety comprising an allele
associated with
increased fertility is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,
90%, 95%,
97%, 99% or 100% identical to that of NP2222, NP2660, NP2276, 1D3461 or a line
described in Table 11.
In some embodiments, the maize plant or plant part is the progeny of an
introgression
wherein the recurrent parent is an elite variety of maize and the donor
comprises an allele
associated with increased fertility. For example, in some embodiments, the
genome of the
recurrent parent is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,
90%, 95%,
97%, 99% or 100% identical to that of NP2222, NP2660, NP2276, NP2391 and/or
NP2460
or a line described in Table 11; and the genome of the donor is at least about
50%, 55%, 60%,
65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% or 100% identical to that of
NP2222,
NP2660, NP2276, 1133461 or a line described in Table 11.
In some embodiments, the maize plant or plant part is the progeny of a cross
between
a first elite variety of maize (e.g., a tester line) and the progeny of a
cross between a second
elite variety of maize (e.g., a recurrent parent) and a variety of maize that
comprises an allele
associated with increased fertility (e.g., a donor). For example, in some
embodiments, the
genome of the first elite variety of maize is at least about 50%, 55%, 60%,
65%, 70%, 75%,
80%, 85%, 90%, 95%, 97%, 99% or 100% identical to that of NP2222, NP2660,
NP2276,
NP2391 and/or NP2460 or a line described in Table 11; the genome of the second
elite
variety of maize is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,
90%, 95%,
97%, 99% or 100% identical to that of NP2222, NP2660, NP2276, NP2391 and/or
NP2460
or a line described in Table 11; and the genome of the variety comprising an
allele associated
with increased fertility is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%,
85%, 90%,
95%, 97%, 99% or 100% identical to that of NP2222, NP2660, NP2276, 1D3461 or a
line
described in Table 11.
In some embodiments, the maize plant or plant part is the progeny of a cross
between
a first elite variety of maize and the progeny of an introgression wherein the
recurrent parent
is a second elite variety of maize and the donor comprises an allele
associated with increased
fertility. For example, in some embodiments, the genome of the first elite
variety of maize is
at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% or
100%
identical to that of NP2222, NP2660, NP2276, NP2391 and/or NP2460 or a line
described in
Table 11; the genome of the recurrent parent is at least about 50%, 55%, 60%,
65%, 70%,
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75%, 80%, 85%, 90%, 95%, 97%, 99% or 100% identical to that of NP2222, NP2660,
NP2276, NP2391 and/or NP2460 or a line described in Table 11; and the genome
of the
donor is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%,
99% or
100% identical to that of NP2222, NP2660, NP2276 or 11)3461 or a line
described in Table
11.
In some embodiments, the maize plant or plant part comprises one or more
transgenes
that encode a gene product that provides resistance to one or more herbicides
(e.g.,
glyphosate, sulfonylurea, imida7olinione, dicamba, glufisinate, phenoxy
proprionic acid,
cycloshexome, traizine, benzonitrile and/or broxyni1).
In some embodiments, the maize plant or plant part comprises one or more
transgenes
that encode a gene product that provides resistance to one or more pests
(e.g., one or more
bacteria, one or more fungi, one or more gastropods, one or more insects, one
or more
nematodes, one or more oomycetes, one or more phytoplasmas, one or more
protozoa and/or
one or more viruses).
In some embodiments, the maize plant or plant part comprises one or more
transgenes
that encode a gene product that provides resistance to one or more diseases.
In some embodiments, the maize plant or plant part expresses one or more Vip3
proteins, for example, comprises a v1p3 transgene in a hemizygous or
homozygous state.
In some embodiments, the maize plant or plant part expresses one or more
nucleic
acids encoding a Vip3 protein (e.g., a Vip3A protein). Then maize plant or
plant part can be
hemizygous or homozygous for the nucleic acid(s) encoding the Vip3 protein(s).
For
example, in embodiments, the plant or plant part is hemizygous or homozygous
for maize
event M1R162. In some embodiments, the maize plant or plant part comprises one
or more
Vip nucleotide sequences as set forth by the accession numbers in Table 4.
In some embodiments, the maize plant or plant part expresses at least one
nucleotide
sequence that is at least about 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,
99.5% or
more identical to one or more of Vip nucleotide sequences as set forth by the
accession
numbers in Table 4.
In some embodiments, the maize plant or plant part expresses at least one
nucleotide
sequence that specifically hybridizes to the nucleotide sequence of one or
more of SEQ ID
NOs: 536 to 601 (as described in Table 4) under stringent hybridization
conditions.
In some embodiments, the maize plant or plant part expresses at least one
nucleotide
sequence that encodes one or more of the Vip amino acid sequences as set forth
by the
accession numbers in Table 4.
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In some embodiments, the maize plant or plant part expresses at least one
nucleotide
sequence that encodes an amino acid sequence that is at least about 75%, 80%,
85%, 90%,
95%, 96%, 97%, 98%, 99%, 99.5% or more identical to one or more of the Vip
amino acid
sequences as set forth by the accession numbers in Table 4.
The present invention extends to plants identified, selected and/or produced
according
to methods of the present invention.
The present invention also extends to products harvested from plants
identified,
selected and/or produced according to methods of the present invention,
including, but not
limited to, plant cells and harvestable plant parts including but not limited
to seeds, leaves,
fruits, flowers, stems.
In some embodiments, the harvested product is a plant cell or plant part
capable of
producing a plant having increased fertility (e.g., increased male fertility).
The present invention also extends to products derived from plants produced
according to methods of the present invention, including, but not limited to,
dry pellets and
powders, oils, fats, fatty acids, starches and proteins.
EXAMPLES
The following examples are not intended to be a detailed catalog of all the
different
ways in which the present invention may be implemented or of all the features
that may be
added to the present invention. Persons skilled in the art will appreciate
that numerous
variations and additions to the various embodiments may be made without
departing from the
present invention. Hence, the following descriptions are intended to
illustrate some particular
embodiments of the invention, and not to exhaustively specify all
permutations, combinations
and variations thereof.
Example!
Development of Mapping Populations
Following the initial discovery of genetic variation in Vip3-induced
reductions in
male fertility, trials were conducted to characterize which inbred maize lines
were most
affected and which inbred maize lines were least affected by Vip3-induced
reduction in male
fertility.
A number of maize inbred lines homozygous for Vip3A (event MIR162) were
evaluated. It was observed that male fertility was reduced in each of the
Vip3A-homozygous
inbred lines tested, albeit to varying degrees. See Table 9 below. Under
normal growth
conditions, some inbred lines (e.g., line NP2222) exhibited minimal reduction
in male
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fertility, while others (e.g., some ID3461 lines) exhibited a significant
reduction in male
fertility. Indeed, several of the Vip3A-homozygous inbred lines (e.g., some
NP2660 and
NP2276 lines) proved to be infertile. The average reduction in male fertility
was
approximately 50%.
Table 5. Vip3A-induced reductions in male fertility vary across genetic
backgrounds.
Pollen Count of Donor Parent Used to Introduce Male
Inbred Line
Vip3A into Inbred Line Fertile?
B14 line 1 good yes
B37 line 1 very poor no
B37 line 2 very good no
B73 line 1 marginal no
B73 line 2 poor no
0H43 line 1 very good yes
Iodent line 1 acceptable no
Iodent line 2 acceptable yes
Iodent line 3 very poor yes
It was observed that the effect of Vip3A expression was mitigated in Vip3A-
hemizygous inbred lines. Inbred lines that were male infertile when homozygous
for Vip3A
were male fertile when hemizygous for Vip3A. Likewise, fertile inbred lines
that exhibited a
significant reduction in male fertility when homozygous for Vip3A were
substantially or
completely male fertile when hernizygous for Vip3A.
It was observed that an increase in environmental stress exacerbated the Vip3A-
induced reductions in male fertility. In particular, it was observed that
Vip3A-induced
reductions in male fertility were more prominent in inbred lines grown under
drought and/or
high temperature conditions (e.g., high daytime temperatures and/or high
nighttime
temperatures). See Fig. 1. Vip3A-induced reductions in male fertility were
also prominent in
inbred lines grown under conditions comprising a large differential between
daytime and
nighttime temperatures. See Fig. 2.
Based upon the foregoing observations, bi-parental F2 mapping populations were
developed by crossing male fertile Vip3A-expressing inbred lines (NP2222 and
ID3461) with
a male infertile Vip3A-expressing inbred line (NP2276) in a reciprocal manner.
Because the
infertile line could not be used as a male when homozygous for Vip3A, the Fl
crosses in
those cases were made by crossing pollen from the corresponding Vip3A-
hemizygous line
onto silks from male fertile inbred lines that were homozygous for Vip3A to
derive the Fl
plants, and then selecting the homozygous Fl plants for making the F2 seed.
All Fl plants
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resulting from the initial crosses were sufficiently male fertile for self-
pollination to make F2
seed.
Example 2
Molecular Marker Analysis and Identification
of OTLs Associated with Increased Male Fertility
Using NP2276 genetics crossed with NP2222 or ID3461 as described in Example 1,
QTLs associated with male fertility were identified. No cytoplasmic effect was
found.
F2 plants derived from the F2 seeds described in Example 1 were field-grown at
Syngenta winter nursery sites in Puerto Rico. Each F2 population consisted of
¨500 plants.
Each plant was phenotyped and/or scored for male fertility as described in
Example 3. Each
plant was tested for zygosity of the vip3A transgene (null, hemizygous,
homozygous) and
confirmed to be expressing the vip3A transgene at a suitable level. Each F2
plant was also
genotyped using ¨200 SNP markers that represented polymorphisms between the
parents and
with the markers spaced across the genome. QTL Cartographer software was used
for
analysis to identify QTLs responsive to the phenotype of interest (increased
male fertility).
The LOD scores for four of the QTLs identified in this study are set forth in
Table 6
below. As shown therein, a QTL identified on chromosome 5 exhibited a strong
association
with increased male fertility.
Table 6. LOD scores of Qlts identified using F2 plants from bi-parental
crosses of NP2222
and NP2276 and bi-parental crosses of ID3461 and NP2276
Chrom NP2276/ NP2222/ NP2222/ NP2276/ ID34611 X0/11)
NP2222 NP2276 NP2276 M3461 NP2276 comb
comb
3 NS 5.8 8.2 7.9 NS 6.2
4 NS 7.4 7.7 (3.6) NS (3.6)
5 11.1 83 19.9 143 13.0 23.1
10 NS 10.9 8.9 6.2 12.3 26.8
LOD significance threshold = 2.5.
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Example 3
PhenotypinE for Increased Male Fertility
To phenotype for increased male fertility, each F2 plant tassel was scored in
the field
for anther quality/ quantity and pollen quantity. Those scores were combined
into a single 1
to 9 Fertility Index score (see Table 7 below; a score of 1 representing the
best fertility and 9
representing infertility). Because pollen quantity is a more relevant measure
of male fertility;
it was weighted more in the derived Fertility Index. Fertility Index scores
were determined
on a daily basis starting the day after a plant began to extrude anthers. On
the first sign of
anther extrusion, the tassel was bagged for scoring on the next two
consecutive days. The
highest fertility score was used in the final data analysis. Inclement weather
sometimes
required skipping a day, but two days of data were always collected on each
plant. Anther
quality was scored on a 1 to 3 scale with 1 being normal anther extrusion
pattern, 2 being
irregular and/or reduced anther extrusion, and 3 being no anther extrusion
(complete male
sterility). Pollen quantity was scored on a relative 1 to 4 scale with 1 being
high pollen
production and 4 being zero pollen production over the 24 hour period.
Segregating Vip3A
parent plants grown in the same field were used as controls to calibrate the
pollen quantity
determinations.
Table 7. Fertility Index used to score F2 plants from bi-parental
crosses of NP2222and NP2276 and hi-parental crosses of ID3461
and NP2276.
Anther Score Pollen Score Fertility Index
1 1 1
2 1
3 1
1 2 2
2 2 3
3 2
1 3 4
2 3 5
3 3 6
1 4 7
2 4 8
3 4 9
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Example 4
Fine Maiming of a 0Th on Chromosome 5
Inbred line NP2276 is normally highly male fertile, but is male infertile when
homozygous for Vip3A. Given this large Vip3A-induced reduction in male
fertility, it was
decided to fine map the QTI. found to have the largest effect in the F2
mapping studies (a
QTL on chromosome 5) to define a smaller interval that could be used for
conversion of other
genetics with this fertility QTL.
Near isogenic lines (NILs) comprising an NP2222-homozygous QTL on chromosome
3 in the NP2276 genetic background were used to fine map the QTL on chromosome
5.
Fl materials from the NP2276 x NP2222 crosses described in Example lwere
backcmssed with NP2276 three times and selfed multiple times with selection
for
maintenance of NP2222 genetics at a QTL on chromosome 3 and maintenance of
both
NP2222 and NP2276 genetics at a QTL on chromosome 5. The remainder of the
genome
outside of those two QTLs was selected for NP2276 genetics as much as
possible. The QTLs
on chromosome 4 and 10 were allowed to segregate back to NP2276 genetics along
with the
rest of the genome.
The finished NILs were grown under normal field conditions at Syngente winter
nursery sites in Puerto Rico. NILs comprising NP2222 genetics at the QTL on
chromosome
3 and the QTL on chromosome 5 exhibited relatively high male fertility,
similar to null
segregates of NP2276. NILs comprising NP2222 genetics at the QTL on chromosome
3 and
NP2276 genetics at the QTL on chromosome 5 were male infertile. Following
multiple
rounds of fine mapping, the QTL on chromosome 5 was iteratively reduced to a
12.13 MB
region bounded by and including positions 72,696,160 and 84,824,203
(chromosomal
segment 190, as described in Table 1).
In greenhouse studies wherein pollen production was quantitated, NILs
comprising
NP2222 genetics at the QTL on chromosome 3 and this smaller QTL on chromosome
5
exhibited male fertility at ¨80% of that measured for wild-type or null
segregates of NP2276.
Example 5
Identification and Fine Mapping of CITLs Associated with Increased Male
Fertility
QTLs associated with increased male fertility were identified and mapped using
the
techniques described above with respect to Examples 1-4.
Examples of the QTLs identified are provided in Table 8.
100
0
Attorney Docket No.: 9207-115W0
Table 8. QTLs associated with increased anther quantity and/or improved anther
quality.
ao
Left Favorable Right Favorable % phenotypic
variation
QTL Chr. cM Marker Position Allele Marker Position Allele Phenotype
LOD score explained
_ 3 3 151.6 1 174825991 _ G 2 195514453 A Anther
Quality 3.2 7.1
Anther Quality!
4-1 4 92.5 3 25326309 G 4 26400247 G Quantity
2.61 7.06
Anther Quality/ Quality-20.8
4-2 4 216.3 5 233629032 A 6 232968070 A Quantity
Quantity-20.3 Quality-32.1 Quanity-32.8
Anther Quality! Quality-90.1 Quality-
56.9
5-1 5 94.9 7 181522829 A 8 77920728 0 Quantity
Quanity-84.85 Quanity-55.7
Anther Quality/ Quality-24.3 Qualiy-
48.3
5-2 5 147.6 9 84824103 T 10 169454950 T Quantity Quanity-
23.3 Quanity-47.9
1.11
00
0
Quality-5.2 Quality-7.8
6 6 189.3 11 165317744 T 12 165632140 G
Anther Quality Quauity-6.1 Quanity-8.8
Anther Quality/ Quality-21.0 Quality-
32.6
7 7 92.2 13 33157904 G 14 52027945 _ A Quantity
Quanthy-202 Quantity-20.2
Anther Quality/ Quality-9.9 Quality-
14.4
_ 9 9 176.8 15 128947590 A 16 147896266 C Quantity
Quanity-9.6 Quanity-14.7
10 192.5 17 142092409 G 18 145273700 0 Anther Quality
325 6.85
LOD significance threshold = 2.5.
ci)
L.)
ni
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Table 9. Design sequences, probes and primers useful to identify the favorable
alleles in the
QTLs described in Table 8
Favorable Design Probe Probe Primer Primer
Cbr QTL Marker Allele (SEQ ID) (SEQ ID) (SEQ ID) (SEQ ID) (SEQ
ID)
3 3 1 G 536 537 538 539 540
3 3 2 A 526 528 530 527 529
4 4-1 3 G 541 542 543 544 545
4 4-1 4 G 546 547 548 549 550
4 4-2 5 A 551 552 553 554 555
4 4-2 6 A 556 557 558 559 560
5-1 7 A 561 562 563 564 565
5 5-1 8 G 566 567 568 569 570
5 5-2 9 T 531 532 534 535 533
5 5-2 10 T 571 572 573 574 575
6 6 11 T 576 577 578 579 580
6 6 12 G 581 582 583
7 7 13 G 584 585 586 587 588
7 7 14 A 589 590 591 592 593
9 9 15 A 594 595 596 597 598
9 9 16 C 599 600 601 602 603
10 17 G 604 605 606 607 608
10 10 18 G 609 610 611 612 613
Inbred line B14 line 1 (see Table 8 above) was observed to comprise alleles
associated with increased male fertility at QTLs on chromosomes 2, 3, 4, 5, 7,
8, 9 and 10.
Inbred lines B37 line 2 and B73 line 2 (see Table 8 above) were observed to
comprise
alleles associated with increased male fertility at a QTL on chromosomes 5, 7
and 9.
The predominant QTL identified in this study, which was centered around
position
81,265,937 on chromosome 5, was finely mapped using a variety of markers and
techniques.
Following multiple rounds of fine mapping, the QTL was iteratively reduced to
a 1.431 MB
region bounded by and including positions 80,804,587 and 82,325,587
(chromosomal
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segment 7514, as described in Table 1). As shown in Table 3, that chromosomal
segment
encodes a number of proteins.
Example 6
Alleles Associated with QTL Intervals
A comparison was made of the SNPs present in inbred maize line NP2222 versus
line
NP2276 across the male fertility-associated QTL intervals in Table 8 above.
The results are
shown in Table 10. Where the alleles differ between the two lines, the NP2222
allele
corresponds to the favorable allele.
The design of assay methods, including the design of suitable primers and
probes, to
detect the presence or absence of the favorable alleles identified in Table 10
in other maize
plants and plant parts is readily apparent to those skilled in the art. For
example, one can
evaluate a sequence extending 5' and/or 3' from the indicated position of each
SNP (e.g., 25,
50, 100, 150, 200, 250 nucleotides or more in the 5' and/or 3' direction) and
use any of a
variety of known software programs to design appropriate amplification primers
and probes
to detect the presence or absence of the favorable allele present in NP2222 in
an
amplification assay.
Table 10. Additional Polymorphisms in Fertility QTLs
QTL Chromosome Nucleotide Position Favorable
3 Chr3 176,322/77 __
3 Chr3 184,155,559
3 Chr3 184,215,519 A
3 Chr3 184,672,762
3 Chr3 185,229,529 A
3 Chr3 186,563,317 A
3 Chr3 187,045,835 A
3 Chr3 188,335,251 A
3 Chr3 189,901,375
_________ 3 Chr3 191,195,919 A
3 Chr3 193,847,182 A
4 1 Chr4 25,639,678
4 1 Chr4 25,988,159 A
4 1 Chr4 26,373,200 A
4 2 Chr4 232,928,019
4 2 Chr4 232,940,724
4 2 Chr4 233,005,187
4_2 Chr4 233,204,685 A
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4 2 Chr4 233,268,189 C
1 Chr5 78,301,966 A
5 1 Chr5 81,454,989 A
51 Chr5 82,952,810 A
5 1 Chr5 83,278,003 A
5_1 AND 5 2 Chr5 86,074,618 C
5 1 AND 5 2 Chr5 92,369,931 A
5 1 AND 5 2 Chr5 99,818,185 A
5_1 AND 52 Chr5 107,477,545 G
5 1 AND 5 2 Chr5 113,579,713 A
5 _1 AND 5_2 Chr5 120,984,518 A
5 1 AND 5 2 Chr5 131,435,275 G
5 1 AND 5 2 Chr5 141,169,239 G
5 1 AND 5 2 Chr5 149,998,432 A
5_i AND 5 2 Chr5 163,409,720 G
5 1 AND 5_2 Chr5 168,858,119 A
5 1 Chr5 170,069,183 A
5 1 Chr5 175,459,402 G
5 1 Chr5 178,321,558 A
6 Chr6 165,353,049 C
6 Chr6 165,632,314 C
_________ 6 Chr6 165,348,117 C
7 Chr7 34,171,694 C
7 Chr7 33,520,778 A
7 Chr7 34,141,494 G
9 Chr9 129,905,275 A
9 Chr9 131,727,013 A
9 Chr9 138,019,524 A
9 Chr9 138,312,159 C
9 Chr9 138,685,900 G
9 Chr9 141,476,864 G
9 Chr9 142,462,911 A
9 Chr9 135,855,445 A
9 Chr9 144,740,620 G
_ Chr10 142,596,522 A
10 _ Chr10 143,063,299 G
_________ 10 Chr10 143,394,664 G
10 _ Chr10 143,663,216 C _
10 _ Chr10 144,109,193 A
10 Chr10 144,314,228 C
10 Chr10 144,741,863 0
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Example?
Other Publicly Available Sources of Favorable Alleles
Using linear regression analysis and pairwise genetic distances, the following
public lines in Table 11 from the Ames Germplasm collection are predicted to
contain the
favorable alleles identified in Table 8 above.
Table 11. Public lines predicted to contain favorable alleles.
Public Lines Probability
Predicted to Have Favorable Allele Other Lines with Global
QTL Favorable Allele Present Similarity
3 A659 65% A73, A660, EP29, W22
4-1 V102 86.8% W8304, W8555
4-2 B103 99.8% 0C4, PHG50, PBP76
PB80, l'X714, NC372, B73,
5-1 NC372, N192, A680 99.7% GEMS-0101, W8304
PB80, TX714, NC372, B73,
5-2 NC372, N192, A680 99.7% GEMS-0101, W8304
B121, B110,NC306,
B104, NC268, NC306, NC268A, NC312, NC308,
6 NC310, NC372 99.8% NC326, PB80, TX714
ND264, S117, M017,
7 ND253, LI152 99.8%, 99.2% M017T,
SeagullSeventeen
R218, R219, VEN981,
________________ 9 Pa762 97% SAN349a-1, 01143T, 01143
DE1 96.2% DE2, PHP02, MS81, MS75
Example 8
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 13 (as described in Table 1) is introgressed from NP2222
into
aVip3A-homozygous inbred line (e.g., a M1R162 inbred line). The introgressed
maize line
exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
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Example 9
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 13 (as described in Table 1) is introgressed from NP2660
into
aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The introgressed
maize line
exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e. g , high daytime and/or nighttime temperatures).
Example 10
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 43 (as described in Table 1) is introgressed from NP2222
into
aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The introgressed
maize line
exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 11
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 43 (as described in Table 1) is introgressed from NP2660
into
aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The introgressed
maize line
exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
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Example 12
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 7514 (as described in Table 1) is introgressed from NP2222
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 13
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 7514 (as described in Table 1) is introgressed from NP2660
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 14
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 7514 (as described in Table 1) is introgressed from NP2276
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
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Example 15
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12747 (as described in Table 1) is introgressed from
NP2222
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 16
Producing Vin3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12747 (as described in Table 1) is introgressed from
NP2660
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 17
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12753 (as described in Table 1) is introgressed from
NP2222
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
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Example 18
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12753 (as described in Table 1) is introgressed from
NP2660
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g, high daytime and/or nighttime temperatures).
Example 19
Producing VM3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12760 (as described in Table 1) is introgressed from
NP2222
into aVip3A-homozygous inbred line (e.g , a MIR.162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
Example 20
Producing Vin3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12760 (as described in Table 1) is introgressed from
NP2660
into aVip3A-homozygous inbred line (e.g., a MIR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g., high daytime and/or nighttime temperatures).
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Example 21
Producing Vip3A-Expressing Maize Plants with Increased Male Fertility
Chromosomal segment 12760 (as described in Table 1) is introgressed from
NP2276
into aVip3A-homozygous inbred line (e.g., a MtR162 inbred line). The
introgressed maize
line exhibits increased male fertility as compared to its recurrent parent. In
particular, the
introgressed maize line exhibits increased pollen production, increased anther
production and
improved anther morphology under normal growth conditions or environmental
stress
conditions (e.g., drought and/or high temperature stress conditions). The
beneficial effects of
the introgressed chromosomal segment are more pronounced in plants grown under
high
temperature conditions (e.g, high daytime and/or nighttime temperatures).
Table 1. Examples of chromosomal segments associated with increased fertility
in maize.
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
1 1 39248635 198733255 28 4 25326309
232968070
2 2 29 4 25326309 233629032
3 3 7411453 168481421 30 4 25326309
238991842
4 3 7411453 174825991 31 4 26400247
182010511
3 7411453 184816495 32 4 26400247 216707012
6 3 7411453 195514453 33 4 26400247
232968070
7 3 7411453 213804184 34 4 26400247
233629032
8 3 168181421 174825991 35 4 26400247
238991842
9 3 168481421 184816495 36 4 182010511
216707012
3 168481421 195514453 37 4 182010511 232968070
11 3 168481421 213804184 38 4 182010511
233629032
12 3 174825991 184816495 39 4 182010511
238991842
13 3 174825991 195514453 40 4 216707012
232968070
14 3 174825991 213804184 41 4 216707012
233629032
3 184816495 195514453 42 4 216707012 238991842
16 3 184816495 213804184 43 4 232968070
233629032
17 3 195514453 213804184 44 4 232968070
238991842
18 4 9852206 25326309 45 4 233629032
238991842
19 4 9852206 26400247 46 5 72696160
73132763
4 9852206 182010511 47 5 72696160 74614332
21 4 98.52206 216707012 48 5 72696160
78022476
22 4 9852206 232968070 49 5 72696160
78023096
23 4 9852206 2336254032 50 5 72696160
78131652
24 4 9852206 238991842 51 5 72696160
78131784
4 25326309 26400247 52 5 72696160 78310499
26 4 25326309 182010511 53 5 72696160
78381593
27 4 25326309 216707012 54 5 72696160
78389884
110
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
._
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Boundary 1 Boundary2 Segment Chn Houndmy1
Boundary2
55 5 72696160 78520683 99 5 72696160 80411639
56 5 72696160 78765635 100 5 72696160 80446855
57 5 72696160 78780292 IOL 5 72696160 80492790
58 5 72696160 78813114 102 5 72696160 80670554
59 5 72696160 78814710 103 5 72696160 80674679
60 5 72696160 78814976 104 5 72696160 80720509
61 5 72696160 78815306 105 5 72696160 80800856
62 5 72696160 78821393 106 5 72696160 80804587
63 5 72696160 78826528 107 5 72696160 80807409
64 5 72696160 78826538 108 5 72696160 80835734
65 5 72696160 78826612 109 5 72696160 80835734
66 5 72696160 78918620 110 5 72696160 80971764
67 3 72696160 78918850 111 5 72696160 80972258
68 5 72696160 79056960 112 5 72696160 80974450
69 5 72696160 79163631 113 5 72696160 81047638
70 5 72696160 79176557 114 5 72696160 81082921
71 5 72696160 79188028 115 5 72696160 81157909
72 5 72696160 79201760 116 5 72696160 81265937
73 5 72696160 79230005 017 5 72696160 81267435
74 5 72696160 79230318 118 5 72696160 81267499
75 5 72696160 79505592 119 5 72696160 81274512
76 5 72696160 79510072 120 5 72696160 81763618
77 5 72696160 79538012 121 5 72696160 81797217
78 5 72696160 79538048 122 5 72696160 81800186
79 5 72696160 79538367 123 5 72696160 81806213
80 5 72696160 79669824 124 5 72696160 81854583
81 5 72696160 79682242 125 5 72696160 81859374
82 5 72696160 79699261 126 5 72696160 81861368
83 5 72696160 79710673 127 5 72696160 81863686
84 5 72696160 79861902 128 5 72696160 81916850
85 5 72696160 79867710 129 5 72696160 81954891
86 5 72696160 79867868 130 5 72696160 81985250
87 5 72696160 79867873 131 5 72696160 82083752
88 5 72696160 79961961 132 5 72696160 82101253
89 5 72696160 80086268 133 5 72696160 82143124
90 5 72696160 80190673 134 5 72696160 82236318
91 5 72696160 80190777 135 5 72696160 82325587
92 5 72696160 80192546 136 5 72696160 82427210
93 5 72696160 80195395 137 5 72696160 82411853
94 5 72696160 80199923 130 5 72696160 82446714
95 5 72696160 80241911 139 5 72696160 82446794
96 5 72696160 80282785 140 5 72696160 82551111
97 5 72696160 80345337 141 5 72696160 82552090
98 5 72696160 80389787 142 5 72696160 82555641
111
,
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chh Bounthry1 Boundary 2 Segment Cht Boundary]
Boundary2
143 5 72696160 82555670 187 5 72696160 84799488
144 5 72696160 12556511 188 5 72696160 84801081
145 5 72696160 82559047 189 5 72696160 84824103
146 5 72696160 82561535 190 5 72696160 84824203
147 5 72696160 82610100 191 5 72696160 84824816
148 5 72696160 82676822 192 5 72696160 84825422
149 5 72696160 82676901 193 5 72696160 84825763
190 5 72696160 82883691 194 5 72696160 84825942
151 5 72696160 82954942 195 5 72696160 84936441
152 5 72696160 82971688 196 5 72696160 84936493
153 5 72696160 83023965 197 5 72696160 84943705
154 5 72696160 83094205 . 198 5 72696160 169454950
155 5 72696160 83146359 199 5 72696160 181522829
156 5 72696160 85280630 200 5 72696160 204759879
157 5 72696160 83281412 201 5 72696160 209874191
158 5 72696160 83400242 202 5 73132763 74614332
159 5 72696160 83405797 203 5 74614332 78022476
160 5 72696160 83437132 204 5 74614332 78023096
161 5 72696160 83522252 205 5 74614332 78131652
162 5 72696160 83560095 206 5 74614332 78131784
163 5 72696160 83560204 207 5 74614332 78310499
164 5 72696160 83572400 208 5 74614332 78381593
165 5 72696160 83607661 209 5 74614332 78389884
166 5 72696160 83745342 210 5 74614332 78520683
167 5 72696160 83861275 211 5 74614332 78765635
168 5 72696160 83861633 212 5 74614332 78780292
169 5 72696160 83865653 213 5 74614332 78813114
170 5 72696160 83865914 214 5 74614332 78814710
171 5 72696160 83865920 215 5 74614332 78814976
172 5 72696160 83868010 216 5 74614332 78815306
173 5 72696160 84019752 217 5 74614332 78821393
174 5 72696160 84065912 218 5 74614332 78826528
175 5 72696160 84086632 219 5 74614332 78826538
176 5 72696160 84089603 220 5 74614332 78826612
177 5 72696160 84104814 221 5 74614332 78918625
178 5 72696160 84105175 222 5 74614332 78918850
179 5 72696160 84251635 223 5 74614332 79056960
180 5 72696160 84252180 224 5 74614332 79163631
181 5 72696160 84253030 225 5 74614332 79176557
182 5 72696160 84254208 226 5 74614332 79188028
183 5 72696160 84314930 227 5 74614332 79201760
184 5 72696160 84340523 228 5 74614332 79230005
185 5 72696160 84516340 229 5 74614332 79230318
186 5 72696160 84706916 230 5 74614332 79505592
112
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Tabk 1 (cont'd.)
Chromosomal Chromosomal
Segment Ow. Boundary 1 Boundary 2 Segment Chr. Bowtdary1
Roundary2
231 5 74614332 79510072 275 5 74614332
81763618
232 5 74614132 79538012 276 5 74614332
81797217
233 5 74614332 79538048 277 5 74614332
81800186
234 5 74614332 79538367 278 5 74614332
81806213
235 5 74614332 79669824 279 5 74614332
81854583
236 5 74614332 79682242 280 5 74614332
81859374
237 5 74614332 79699261 281 5 74614332
81861368
238 5 74614332 79710673 262 5 74614332
81863686
239 5 74614332 79861902 283 5 74614332
81916850
240 5 74614332 79867710 284 5 74614332
81954891
241 5 74614332 79867868 285 5 74614332
81985250
242 5 74614332 79867873 286 5 74614332
82083752
243 5 74614332 79961961 287 5 74614332
82101253
244 5 74614332 80086268 288 5 74614332
82143124
245 5 74614332 80190673 289 5 74614332
82236318
246 5 74614332 80190777 295 5 74614332
82325587
247 5 74414332 30192546 291 5 74614332
12427210
248 5 74614332 80195395 292 5 74614332
82431053
249 5 74614332 80199923 293 5 74614332
82446714
250 5 74614332 80241911 294 5 74614332
82446794
251 5 74614332 80282785 295 5 74614332
82551111
252 5 74614332 80345337 296 5 74614332
82552090
253 5 74614332 80389787 297 5 74614332
82555641
254 5 74614332 80411639 298 5 74614332
82555670
255 5 74614332 80446855 299 5 74614332
82556511
256 5 74614332 80492790 300 5 74614332
82559047
257 5 74614332 80670554 301 5 74614332
82561535
258 5 74614332 80674679 302 5 74614312
82610100
259 5 74614332 80720509 303 5 74614332
82676822
260 5 74614332 80800856 304 5 74614332
82676901
261 5 74614332 80804587 305 5 74614332
82883691
262 5 74614332 10807409 306 5 74614332
82954942
263 5 74614332 80835734 307 5 74614332
82971688
264 5 74614332 80835734 308 5 74614332
83023965
265 5 74614332 80971764 309 5 74614332
83094205
266 5 74614332 80972258 310 5 74614332
83146355
267 5 74614332 80974450 311 5 74614332
83280630
268 5 74614332 81047638 312 5 74614332
83281412
269 5 74614332 81082921 313 5 74614332
83400242
270 5 74614332 81157909 214 5 74614332
83405797
271 5 74414332 81265937 315 5 74614332
83437132
272 5 74614332 81267485 316 5 74614332
83522252
273 5 74614332 81267499 317 5 74614332
83560095
274 5 74614332 81274512 318 5 74614332
83560204
. 113
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Boundary 1 Boundary 2 ScgmeM Chr. Boundary 1
Boundary 2
319 5 74614332 83572400 363 5 74614332 78389884
320 5 74614332 83607661 364 5 74614332 78520683
321 5 74614332 83745342 365 5 74614332 78765635
322 5 74614332 83861275 366 5 74614332 78780292
323 5 74614332 83861633 367 5 74614332 78813114
324 5 74614332 83865653 368 5 74614332 78814710
325 5 74614332 83865914 369 5 74614332 78814976
326 5 74614332 83865920 370 5 74614332 78815306
327 5 74614332 83868010 371 5 74614332 78821393
328 5 74614332 84019752 372 5 74614332 78826528
329 5 74614332 84065912 373 5 74614332 78826538
330 5 74614332 84086632 374 5 74614332 78826612
331 5 74614332 84089603 375 5 74614332 78918620
332 5 74614332 84104814 376 5 74614332 78918850
333 5 74614332 84105175 377 5 74614332 79056960
334 5 74614332 84251635 378 5 74614332 79163631
335 5 74614332 84252180 379 5 74614332 79176557
336 5 74614332 84253030 380 5 74614332 79188028
337 5 74614332 8.4254208 381 5 74614332 79201760
338 5 74614332 84314930 382 5 74614332 79230005
339 5 74614332 84340523 383 5 74614332 79230318
340 5 74614332 84516340 384 5 74614332 79505592
341 5 74614332 84706916 385 5 74614332 79510072
342 5 74614332 84799488 386 5 74614332 79538012
343 5 74614332 84801081 387 5 74614332 79538048
344 5 74614332 84824101 388 5 74614332 79538367
345 5 74614332 84824203 389 5 74614332 79669824
346 5 74614332 84824816 390 5 74614332 79682242
347 5 74614332 84825422 ' 391 5 74614332 79699261
348 5 74614332 84825763 392 5 74614332 79710673
349 5 74614332 84825942 393 5 74614332 79861902
350 5 74614332 84936441 394 5 74614332 79867710
351 5 74614332 84936493 395 5 74614332 79867868
352 5 74614332 84943705 396 5 74614332 79867873
353 5 74614332 169454950 397 5 74614332 79961961
354 5 74614332 181522829 398 5 74614332 80086268
355 5 74614332 204759879 399 5 74614332 80190673
356 5 74614332 209874191 400 5 74614332 80190777
397 5 74614332 78022476 401 5 74614332 80192546
358 5 74614332 78023096 402 5 74614332 80195395
359 5 74614332 78131652 403 5 74614332 80199923
360 5 74614332 78131784 404 5 74614332 80241911
361 5 74614332 78310499 405 5 74614332 80282785
362 5 74614112 78381593 406 5 74614332 80345337
114
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chmmommal
Segment Clr. Boundaryl Boundary2 Segment CIL Boundaryl
Boundary 2
407 5 74614332 80389787 451 5 74614332 82555641
408 5 74614332 80411639 452 5 74614332 82555670
409 5 74614332 80446855 453 5 74614332 82556511
410 5 74614332 80492790 454 5 74614332 82559047
411 5 74614332 80670554 455 5 74614332 82561535
412 5 74614332 80674679 456 5 74614332 82610100
413 5 74614332 80720509 457 5 74614332 82676822
414 5 74614332 80800856 458 5 74614332 82676901
415 5 74614332 80804587 459 5 74614332 82883691
416 5 74614332 80807409 460 5 74614332 82954942
417 5 74614332 80835734 461 5 74614332 82971688
418 5 74614332 80835734 462 5 74614332 83023965
419 5 74614332 80971764 463 5 74614332 83094205
420 5 74614332 80972258 464 5 74614332 83146355
421 5 74614332 80974450 465 5 74614332 83280630
422 5 74614332 81047638 466 5 74614332 83281412
423 5 74614332 81082921 467 5 74614332 83400242
424 5 74614332 81157909 468 5 74614332 83405797
425 5 74614332 81265937 469 5 74614332 83437132
426 5 74614332 81267485 470 5 74614332 83522252
427 5 74614332 81267499 471 5 74614332 83560095
428 5 74614332 81274512 472 5 74614332 83560204
429 5 74614332 81763618 473 5 74614332 83572400
430 9 74614332 81797217 474 5 74614332 83607661
431 5 74614332 81800186 475 5 74614332 83745342
432 5 74614332 81806213 476 5 74614332 83861275
433 5 74614332 81854583 477 5 74614332 83861633
434 5 74614332 81859374 478 5 74614332 83865653
435 5 74614332 81861368 479 5 74614332 83865914
436 5 74614332 81863686 480 5 74614332 83865920
437 5 74614332 81916850 481 5 74614332 83868010
438 5 74614332 81954891 482 5 74614332 84019752
439 5 74614332 81985250 483 5 74614332 84065912
440 5 74614332 82083752 484 5 74614332 = 84086632
441 5 74614332 82101293 485 5 74614332 84089603
442 5 74614332 82143124 486 5 74614332 84104814
443 5 74614332 82236318 487 5 74614332 84105175
444 5 74614332 82325587 488 5 74614332 84251635
445 5 74614332 82427210 489 5 74614332 84252180
446 5 74614332 82431853 490 5 74614332 84253030
447 5 74614332 82446714 491 5 74614332 84254208
448 5 74614332 82446794 492 5 74614332 84314930
449 5 74614332 82551111 493 5 74614332 84340523
450 5 74614332 82552090 494 5 74614332 84516340
115
CA 02 939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Cho. Boundary!
Boundary 2
495 5 74614332 84706916 539 5 77920728
79510072
496 5 74614332 94799488 540 5 77920728
79538012
497 5 74614332 84801081 541 5 77920728
79538048
498 5 74614332 84824103 542 5 77920728
79538367
499 5 74614332 84824203 543 5 77920728
79669824
500 5 74614332 84824816 544 5 77920728
79682242
501 5 74614332 84825422 545 5 77920728
79699261
502 5 74614332 84825763 546 5 77920728
79710673
503 5 74614332 84825942 547 5 77920728
79861902
504 5 74614332 84936441 548 5 77920728
79867710
505 5 74614332 84936493 549 5 77920728
7986786!
506 5 74614332 84943735 550 5 77920728
79867873
507 5 74614332 169454950 551 5 77920728
79961961
508 5 74614332 181522829 552 5 77920728
80086268
509 5 74614332 204759879 553 5 77920728
80190673
510 5 74614332 209874191 554 5 77920728
80190777
511 5 77920728 78022476 555 5 77920728
80192546
512 5 77920728 78023096 556 5 77920728
80195395
513 5 77920728 78131652 557 5 77920728
80199923
514 5 77920728 78131784 558 5 77920728
80241911
515 5 77920728 78310499 559 5 77920728
80282785
516 5 77920728 78381593 560 5 77920728
80345337
517 5 77920728 78389884 561 5 77920728
80389787
518 5 77920728 78520683 562 5 77920728
80411639
519 5 77920728 78765635 563 5 77920728
80446855
520 5 77920728 78780292 564 5 77920728
80492790
521 5 77920728 78813114 565 5 77920728
80670554
522 5 77920728 78814710 566 5 77920728
80674679
523 5 77920728 78814976 567 5 77920728
80720509
524 5 77920728 78815306 568 5 77920728
80800856
525 5 77920728 78821393 569 5 7792072!
80804587
526 5 77920728 78826528 570 5 77920728
00807409
527 5 77920728 78826538 571 5 77920728
80835734
528 5 77920728 78826612 572 5 77920728
80835734
529 5 77920728 78918620 573 5 77920728
80971764
530 5 77920728 78918850 574 5 77920728
80972258
531 5 77920728 79056960 575 5 77920728
80974450
532 5 77920728 79163631 576 5 77920728
81047638
533 5 77920728 79176557 577 5 77920728
81082921
534 5 77920728 79188028 578 5 77920728
81157909
535 5 77920728 79201760 579 5 77920728
81265937
536 5 77920728 79230005 580 5 77920728
81265937
537 5 77920728 79230318 581 5 77920728
81267485
538 5 77920728 79505592 582 5 77920728
81267499
116
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chnnnonomal Chromosomn1
Segment Chi. Boundaryl Boundary2 Segment Chi. Boundaryl
Boundary 2
583 5 77920728 81274512 627 5 77920728
83560204
584 5 77920728 81763618 628 5 77920728
83572400
585 5 77920728 81797217 629 5 77920728
83607661
586 5 77920728 81800186 630 5 77920728
83745342
587 5 77920728 81806213 631 5 77920728
83861275
588 5 77920728 81854583 632 5 77920728
83861633
589 5 77920728 81859374 633 5 77920728
83865653
590 5 77920728 81861368 634 5 77920728
83865914
591 5 77920728 11863686 635 5 77920728
83865920
592 5 77920728 81916850 636 5 77920728
83868010
593 5 77920728 81954891 637 5 77920728
84019752
594 5 77920728 81985250 638 5 77920728
84065912
595 5 77920728 82083752 639 5 77920728
84086632
596 5 77920728 82101253 640 5 77920728
84089603
597 5 77920728 82143124 641 5 77920728
84104814
598 5 77920728 82236318 642 5 77920728
84105175
599 5 77920728 82325587 643 5 77920728
84251635
600 5 77920728 82427210 644 5 77920728
84252180
601 5 77920728 82431853 645 5 77920720
84253030
602 5 77920728 82446714 646 5 77920728
84254208
603 5 77920728 82446794 647 5 77920728
84314930
604 5 77920728 82551111 648 5 77920728
84340523
605 5 77920728 82552090 649 5 77920728
84516340
606 5 77920728 82555641 650 5 77920728
84706916
607 5 77920728 82555670 651 5 77920728
84799488
608 5 77920728 82556511 652 5 77920728
84801081
609 5 77920728 82559047 653 5 77920728
84824103
610 5 77920728 82561535 654 5 77920728
84824103
611 5 77920728 82610100 655 5 77920728
84824203
612 5 77920728 82676822 656 5 77920728
84824816
613 5 77920728 82676901 657 5 77920728
84825422
614 5 77920728 82883691 658 5 77920728
84825763
615 5 77920728 82954942 659 5 77920728
84825942
616 5 77920728 82971688 660 5 77920728
84936441
617 5 77920728 83023965 661 5 77920728
84936493
618 5 77920728 83094205 662 5 77920728
84943705
619 5 77920728 83146355 663 5 77920728
169454950
620 5 77920728 83280630 664 5 77920728
181522829
621 5 77920728 83281412 665 5 77920728
204759879
622 5 77920728 83400212 666 5 77920728
209874191
623 5 77920728 83405797 667 5 78022476
78023096
624 5 77920728 83437132 668 5 78022476
78131652
625 5 77920728 83522252 669 5 78022476
78131784
626 9 77920728 83560095 670 5 78022476
78310199
117
CA 02 939580 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cent' d.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
671 5 78022476 78381593 715 5 78022476 80345337
672 5 78022476 78389884 716 5 78022476 80389787
673 5 78022476 78520683 717 5 78022476 80411639
674 5 78022476 78765635 718 5 78022476 80446855
675 5 78022476 78780292 719 5 78022476 80492790
676 5 78022476 78813114 720 5 78022476 80670554
677 5 78022476 78814710 721 5 78022476 80674679
678 5 78022476 78814976 722 5 78022476 80720509
679 5 78022476 78815306 723 5 78022476 80000856
680 5 78022476 78821393 724 5 78022476 80804587
681 5 78022476 78826528 725 5 78022476 80807409
682 5 78022476 78826538 726 5 78022476 80835734
683 5 78022476 78826612 727 5 78022476 80835734
684 5 78022476 78918620 728 5 78022476 80971764
685 5 78022476 78918850 729 5 70022476 80972258
686 5 78022476 79056960 730 5 78022476 80974450
687 5 78022476 79163631 731 5 78022476 81047638
688 5 78022476 79176557 732 5 78022476 81082921
689 5 78022476 79188028 733 5 78022476 81157909
690 5 78022476 79201760 734 5 78022476 81265937
691 5 78022476 79230005 735 5 78022476 81265937
692 5 78022476 79230318 736 5 78022476 81267485
693 5 78022476 79505592 737 5 78022476 81267499
694 5 78022476 79510072 738 5 78022476 81274512
695 5 78022476 79538012 739 5 78022476 81763618
696 5 78022476 79538048 740 5 78022476 81797217
697 5 78022476 79538367 741 5 78022476 81800186
698 5 78022476 79669824 742 5 78022476 81806213
699 5 78022476 79682242 743 5 78022476 81854583
700 5 78022476 79699261 744 5 78022476 81859374
701 5 78022476 79710673 745 5 78022476 81861368 '
702 5 78922476 79861902 746 5 78022476 81863686
703 5 78022476 79867710 747 5 78022476 81916850
704 5 78022476 79867868 748 5 78022476 81954891
705 5 78022476 79867873 749 5 78022476 81985250
706 5 78022476 79961961 750 5 78022476 82083752
707 5 78022476 80086268 751 5 78022476 82101253
708 5 78022476 80190673 752 5 78022476 82143124
709 5 78022476 80190777 753 5 78022476 82236318
710 5 78022476 80192546 754 5 78022476 82325587
711 5 78022476 80195395 755 5 78022476 82427210
712 5 78022476 80199923 756 5 78022476 82431853
713 5 78022476 80241911 757 5 78022476 82446714
714 5 78022476 80282785 758 5 78022476 82446794
118
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'cL)
Chromosomal Chromosomal
Segment CM. Boundari1 Boundary2 Segment Cite. Boundaryl Boundary2
759 5 78022476 82551111 803 5 78022476
84340523
760 5 78022476 82552090 804 5 78022476
84516340
761 5 78022476 82555641 805 5 78022476
84706916
762 5 78022476 82555670 806 5 78022476
84799488
763 5 76022476 82556511 807 5 78022476
84801081
764 5 78022476 82559047 808 5 78022476
84824103
765 5 78022476 82561535 809 5 78022476
84824203
766 5 78022476 82610100 810 5 78022476
84824816
767 5 78022476 92676822 811 5 78022476
84825422
768 5 78022476 82676901 812 5 78022476
84825763
769 5 78022476 82883691 813 5 78022476
84825942
770 5 78022476 82954942 814 5 78022476
84936441
771 5 78022476 82971688 815 5 78022476
84936493
772 5 78022476 83023965 816 5 78022476
84943705
773 5 78022476 83094205 817 5 78022476
169454950
774 5 78022476 83146355 818 5 78022476
181522829
775 5 78022476 83280630 819 5 78022476
204759879
776 5 78022476 83281412 820 5 78022476
209874191
777 5 78022476 83.400242 821 5 78129898
78111652
778 5 78022476 83405797 822 5 78129898
78131784
779 5 78022476 83437132 823 5 78129898
78310199
780 5 78022476 83522252 824 5 78129898
78381593
781 5 78022476 83560095 825 5 78129898
78389884
782 5 78022476 83560204 826 5 78129898
78520683
783 5 78022476 83572400 827 5 78129898
78765635
784 5 78022476 83607661 828 5 78129898
78780292
785 5 78022476 83745342 829 5 78129898
78813114
786 5 78022476 83861275 830 5 78129898
78814710
787 5 78022476 83861633 831 5 78129898
78814976
788 5 78022476 83865653 832 5 78129898
78815106
789 5 78022476 83865914 033 5 78129898
78821393
790 5 78022476 83865920 834 5 78129898
78826528
791 5 78022476 83868010 835 5 78129898
7E826538
792 5 78022476 84019752 836 5 78129898
78826612
793 5 78022476 84065912 837 5 78129898
78918620
794 5 78022476 84086632 838 5 78129898
78918850
795 5 78022476 84089603 839 5 78129898
79056960
796 5 78022476 84104814 840 5 78129898
79163631
797 5 78022476 84105175 841 5 78129898
79176557
798 5 78022476 84251635 842 5 78129898
79188628
799 5 78022476 84252180 843 5 78129898
79201760
800 5 78022476 84253030 844 5 78129898
79230005
801 5 78022476 84254208 845 5 78129898
79230318
802 5 78022476 84314930 846 5 78129898
79505592
119
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Boundary 1 Boundary2 Segment Chr. Boundary1
Boundary2
847 5 78129898 79510072 891 5 78129898
81763618
848 5 78129898 79538012 892 5 78129898
81797217
849 5 78129898 79538048 893 5 78129898
81800186
850 5 78129898 79538367 894 5 78129898
81806213
851 5 78129898 79669824 895 5 78129898
61854583
852 5 78129898 79682242 896 5 78129898
81859374
853 5 78129898 79699261 897 5 78129898
81861368
854 5 78129898 79710673 898 5 78129898
81863686
855 5 78129898 79861902 899 5 78129898
81916850
956 5 78129898 79867710 900 5 78129898
81954891
857 5 78129898 79867868 901 5 78129898
81985250
858 5 78129898 79867873 902 5 78129898
82083752
859 5 78129898 79961961 903 5 78129898
82101253
860 5 78129898 80086268 904 5 78129898
82143124
861 5 78129898 80190673 905 5 78129898
82236318
862 5 78129898 80190777 906 5 78129898
82325587
863 5 78129898 80192546 907 5 78129898
82427210
864 5 78129898 80195395 908 5 78129898
82431853
865 5 78129898 80199923 909 5 78129898
82446714
866 5 78129898 80241911 910 5 78129898
82446794
867 5 78129898 80282785 911 5 78129898
82551111
868 5 78129898 80345337 912 5 78129898
82552090
869 5 78129898 80389787 913 5 78129898
82555670
870 5 78129898 80411639 914 5 78129898
82555670
871 5 78129898 80446855 915 5 78129898
82556511
872 5 78129898 80492790 916 5 78129898
82559047
873 5 78129898 80670554 917 5 78129898
82561535
874 5 78129898 80674679 918 5 78129898
82610100
875 5 78129898 80720509 919 5 78129898
82676822
876 5 78129898 80800856 920 5 78129898
82676901
877 5 78129898 80804587 921 5 78129898
82883691.
878 5 78129898 80807409 922 5 78129098
82954942
879 5 78129898 80835734 923 5 78129898
82971688
880 5 78129898 80971764 924 5 78129898
83023965
881 5 78129898 80972258 925 5 78129898
83094205
882 5 78129898 80974450 926 5 78129898
83146355
88.3 5 78129898 81047638 927 5 78129898
83280630
884 5 78129898 81082921 928 5 78129898
83281412
885 5 78129898 81157909 929 5 78129898
83400242
886 5 78129898 81265937 930 5 78129898
83405797
887 5 78129898 81265937 931 5 78129898
83437132
888 5 78129898 0.1267485 932 5 78129898
83522252
889 5 78129898 81267499 933 5 78129898
83560095
890 5 78129898 81274512 934 5 78129898
83560204
120
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosome! Chromosomal
Segment Chn Boundary1 Boundary2 Segment Chu. Bounclary1 Boundary2
935 5 78129898 83572400 979 5 78255163
78780292
936 5 78129898 83607661 980 5 78255163
78813114
937 5 78129898 83745342 961 5 78255163
78814710
938 5 78129898 83861275 982 5 78255163
78814976
939 5 78129898 83861633 983 5 78255163
78815306
940 5 78129898 83865653 984 5 78255163
78821393
941 5 78129898 83865914 985 5 78255163
78826528
942 5 78129898 83865920 986 5 78255163
78826538
943 5 78129898 83868010 987 5 78255163
78826612
944 5 78129898 84019752 988 5 78255163
76918620
945 5 78129898 84065912 989 5 78255163
78918850
946 5 78129898 84086632 990 5 78255163
79056960
947 5 78129898 84089603 991 5 78255163
79163631
948 5 78129898 84104814 992 5 78255163
79176557
949 5 78129898 84105175 993 5 78255163
79188028
950 5 78129898 84251635 994 5 78255163
79201760
951 5 78129898 84252180 995 5 78255163
79230005
952 5 78129898 84253030 996 5 78255163
79230318
953 5 78129898 84254208 997 5 78255163
79505592
954 5 78129898 84314930 998 5 78255163
79510072
955 5 78129898 84340523 999 5 78255163
79538012
956 5 78129898 84516340 1000 5 78255163
79538048
957 5 78129898 84706916 1001 5 78255163
79538367
958 5 78119898 84799488 1002 5 78255163
79669824
959 5 78129898 84801081 1003 5 78255163
79682242
960 5 78129898 84824103 1004 5 78255163
79699261
961 5 78129898 84824203 1005 5 78255163
79710673
962 5 78129898 84824816 1006 5 78255163
79861902
963 5 78129898 84825422 1007 5 78255163
79867710
964 5 78129898 84825763 1008 5 78255163
79867868
965 5 78129898 84825942 1009 5 78255163
79867873
966 5 78129898 84843411 1010 5 78255163
79961961
967 5 78129898 81936441 1011 5 78255163
80086268
968 5 78129898 84936493 1012 5 78255163
80190673
969 5 78129898 84943705 1013 5 78255163
80190777
970 5 78129898 169454950 1014 5 78255163
80192546
971 5 78129898 181522829 1015 5 78255163
80195395
972 5 78129898 104759879 1016 5 78255163
80199923
973 5 78129898 209874191 1017 5 78255163
80241911
974 5 78255163 78310499 1018 5 78255163
80282785
975 5 78255163 78381593 1019 5 78255163
80345337
976 5 78255163 78389884 1020 5 78255163
80389787
977 5 78255163 78520683 1021 5 78255163
80411639
978 5 78255163 78765635 1022 5 78255163
80446855
121
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
.. =
Table 1 (contd.)
Chromosomal Chromosomal
Segment (Sir. Buendary1 Boundary2 Segment Chr. Boundary1 Boundary2
1023 5 78255163 80492790 1067 5 78255163
82559047
1024 5 78255163 80670554 1068 5 78255163
82561535
1025 5 78255163 80674679 1069 5 78255163
82610100
1026 5 78255163 80720509 1070 5 78255163
82676822
1027 5 78255163 80800856 1071 5 78255163
82676901
1028 5 78255163 80804587 1072 5 78255163
82883691
1029 5 78255163 80807409 163 5 78255163
82954942
1030 5 78255163 80835734 1074 5 78255163
82971688
1031 5 78255163 80971764 1075 5 78255163
83023965
1032 5 78255163 80972258 1076 5 78255163
83094205
1033 5 78255163 80974450 1077 5 78255163
83146355
1034 5 78255163 81047638 1078 5 78255163
83280630
1035 5 70255163 81082921 1079 5 78255163
83281412
1036 5 78255163 81157909 1080 5 78255163
83400242
1037 5 78255163 81265937 1081 5 78255163
83405797
1038 5 78255163 81265937 1082 5 78255163
83437132
1039 5 78255163 81267485 1083 5 78255163
83522252
1040 5 78255163 81267499 1084 5 78255163
83560095
1041 5 78255163 81274512 1085 5 78255163
83560204
1042 5 78255163 81763618 1086 5 78255163
83572400
1043 5 78255163 81797217 1087 5 78255163
83607661
1044 5 78255163 81800186 1088 5 78255163
83745342
1045 5 78255163 81806213 1089 5 78255163
83861275
1046 5 70255163 81854583 1090 5 78255163
83861633
1047 5 78255163 81859374 1091 5 78255163
83865653
1048 5 78255163 811161368 1092 5 78255163
83865914
1049 5 78255163 81863686 1093 5 78255163
83865920
1050 5 78255163 81916850 1094 5 78255163
831168010
1051 5 78255163 81954891 1095 5 78255163
84019752
1052 5 78255163 81985250 1096 5 78255163
84065912
1053 5 78255163 82083752 1097 5 78255163
84086632
1054 5 78255163 82101253 1098 5 78255163
84089603
1055 5 78255163 82143124 1099 5 78255163
84104814
1056 5 78255163 82236318 1100 5 78255163
84105175
1057 5 78255163 82325587 1101 5 78255163
84251635
1058 5 78255163 82427210 1102 5 78255163
84252180
1059 5 78255163 82431853 1103 5 78255163
84253030
1060 5 78255163 82446714 1104 5 78255163
84254208
1061 5 78255163 82446794 1105 5 78255163
84314930
1062 5' 78255163 82551111 1106 5 78255163
84340523
1063 5 78255163 82552090 1107 5 78255163
84516340
1064 5 78255163 82555641 1108 5 78255163
84706916
1065 5 78255163 82555670 1109 5 78255163
84799488
1066 5 78255163 82556511 1110 5 78255163
84801081
122
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Clwornosornal Chromosomal
Segment Cir. Boundaryl Bousdary2 Segment Chr. Boundary1 Boundani2
1111 5 78255163 84824103 1155 5 78380304
79699261 .
1112 5 78255163 84824203 1156 5 78380304
79710673
1113 5 78255163 84824816 1157 5 78380304
79861902
1114 5 78255163 84825422 1158 5 78380304
79867710
1115 5 78255163 84925763 1159 5 783180304
79867868
1116 5 78255163 84825942 1160 5 78380304
79867873
1117 5 78255163 84843411 1161 5 78380304
79961961
1118 5 78255163 84936441 1162 5 78380304
80086268
1119 5 78255163 84936493 1163 5 78380304
80190673
1120 5 78259163 84943705 1164 5 78380304
80190777
1121 5 78255163 169454950 1165. 5 78380304
80192546
1122 5 78255163 . 181522829 1166 5 78380304 80195395
1123 5 78255163 204759879 1167 5 78380304
80199923
1124 5 78255163 209874191 1168 5 78380304
80241911
1125 5 78380304 78381593 1169 5 78380304
80282785
' 1126 5 78380304 78389884 1170 5 78380304
80345337
1127 5 78380304 78520683 1171 5 711380304
80389787
1128 5 78380304 78765635 1172 5 78380304
80411639
1129 5 78380304 78780292 1173 5 78380304
80446855
1130 5 78380304 78813114 1174 5 78380304
80492790
1131 5 78380304 78814710 1175 5 78380304
80670554
1132 5 78380304 78814976 1176 5 78380304
80674679
1133 5 78380304 78815306 1177 5 78380304
80720509
1134 5 78380304 78821393 1178 5 78380304
80800856
1135 5 78380304 78826528 1179 5 78380304
80804587
1136 5 78380304 78826538 1180 5 78380304
80807409
1137 5 78380304 78826612 1181 5 78380304
80835734
1138 5 78380304 78918620 1182 5 78380304
80971764
1139 5 78380304 78918850 1183 5 78380304
80972258
1140 5 78380304 79056960 1184 5 78380304
80974450
1141 5 78380304 79163631 1185 5 78380304
81047636
1142 5 78380304 79176557 1186 5 78380304
81082921
1143 5 78380304 79188028 1187 5 78380304
81157909
1144 5 78380304 79201760 1188 5 78380304
81265937
1145 5 78380304 79230005 1189 5 78380304
81265937
1146 5 78380304 79230318 1190 5 78380304
81267485
1147 5 78380304 .79505592 1191 5 78380304
81267499
1148 5 78380304 79510072 1192 5 78380304
81274512
. 1149 5 78380304 79538012 1193 5 78380304 81763618
1150 5 78380304 79538048 1194 5 78380304
81797217
1151 5 78380304 79538048 1195 5 78380304
81800186
1152 5 78380304 79538367 1196 5 78380304
81806213 _
1153 5 78380304 79669824 1197 5 78380304
81854583
1154 5 78380304 79682242 1198 5 78380304
81859374
123
CA 02 93 9580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'cL)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
1199 5 78380304 81861368 1243 5 78380304 83865914
1200 5 78380304 81863686 1244 5 78380304 83865920
1201 5 78380304 81916850 1245 5 78380304 83868010
1202 5 78380304 81954891 1246 5 78380304 84019752
1203 5 78380304 81985250 1247 5 78380304 84065912
1204 5 78380304 82083752 1248 5 78380304 84086632
1205 5 78380304 82101253 1249 5 78380304 84089603
1206 5 78380304 82143124 1250 5 78380304 84104814
1207 5 78380304 82236318 1251 5 78380304 84105175
1208 5 78380304 82325587 1252 5 78380304 84251635
1209 5 78380304 82427210 1253 5 78380304 84252180
1210 5 78380304 82431853 1254 5 78380304 84253030
1211 5 70380304 82446714 1255 5 78380304 84254208
1212 5 78380304 82446794 1256 5 78380304 84314930
1213 5 78380304 82551111 1257 5 78380304 84340523
1214 5 78380304 82552090 1258 5 78380304 84516340
1215 5 78380304 82555641 1259 5 78380304 84706916
1216 5 78380304 82555670 1260 5 78380304 84799488
1217 5 78380304 82556511 1261 5 78380304 84801081
1218 5 78380304 82559047 1262 5 78380304 84824103
1219 5 78380304 82561535 1263 5 78380304 84824203
1220 5 78380304 82610100 1264 5 78380304 84824816
1221 5 78380304 82676822 1265 5 78380304 84825422
1222 5 78380304 82676901 1266 5 78380304 84825763
1223 5 78380304 82883691 1267 5 78380304 84825942
1224 5 78380304 82954942 1268 5 78380304 84843411
1225 5 78380304 82971688 1269 5 78380304 84936441
1226 5 78380304 83023965 1270 5 78380304 84936493
1227 5 78380304 83094205 1271 5 78380304 84943705
1228 5 78380304 83146355 1272 5 78380304 169454950
1229 5 78380304 83280630 1273 5 78380304 181522829
1230 5 78380304 83281412 1274 5 78380304 204759879
1231 5 78380304 83400242 1275 5 78380304 209874191
1232 5 78380304 83405797 1276 5 78381834 78389884
1233 5 78380304 83437132 1277 5 78381834 78520683
1234 5 78380304 83522252 1276 5 78381834 78765635
1235 5 78380304 83560095 1279 5 78381834 78780292
1236 5 78380304 83560204 1280 5 78381834 78813114
1237 5 78380304 83572400 1281 5 78381834 78814710
1238 5 78380304 83607661 1282 5 78381834 78814976
1239 5 78380304 83745342 1283 5 78381834 78815306
1240 5 78380304 83861275 1284 5 78381834 78621393
1241 5 78380304 83861633 1285 5 78381834 78826528
1242 5 78380304 83865653 1286 5 78381834 78826538
124
CA 02 93 9580 2 0 16-08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary! Boundary 2 Segment Chr Boundary 1
Boundary 2
1287 5 78381834 78826612 1331 5 78381834 80971764
1288 5 78381834 78918620 1332 5 78381834 80972258
1289 5 78381834 78918850 I 333 5 78381834 80974450
1290 5 78381834 79056960 1334 5 78381834 81047638
1291 5 78381834 79163631 1335 5 78381834 81082921
1292 5 78381834 79176557 1336 5 78381834 81157909
1293 5 78381834 79188028 1337 5 78381834 81265937
1294 5 78381834 79201760 1338 5 78381834 81265937
1295 5 78381834 79230005 1339 5 78381834 81267485
1296 5 78381834 79230318 1340 5 78381834 81267499
1297 5 78381834 79505592 1341 5 78381834 81274512
1298 5 78381834 79510072 1342 5 78381834 81763618
1299 5 78381834 79538012 1343 5 78381834 81797217
1300 5 78381834 79538048 1344 5 78381834 81800186
1301 5 78381834 79538367 1345 5 78381834 81806213
1302 5 78381834 79669824 1346 5 78381834 81854583
1303 5 78381834 79682242 1347 5 78381834 81859374
1334 5 78381834 79699261 1348 5 78381834 81861368
1305 5 78381834 79710673 1349 5 78381834 81863686
1306 5 78381834 79861902 1350 5 78381834 81916850
1307 5 78381834 79867710 1351 5 78381834 81954891
1308 5 78381834 79867868 1352 5 78381834 81985250
1309 5 78381834 79867873 1353 5 78381834 82083752
1310 5 78381834 79961961 1354 5 78381834 82101253
1311 5 78381834 80086268 1355 5 78381834 82143124
1312 5 78381834 80190673 1356 5 78381834 82236318
1313 5 78381834 80190777 1357 5 78381834 82325587
1314 5 78381834 80192546 1358 5 78381834 82427210
1315 5 78381834 80195395 1359 5 78381834 82431853
1316 5 78381834 80199923 1360 5 78381834 82446714
1317 5 78381834 80241911 1361 5 78381834 82446794
1318 5 78381834 80282785 1362 5 78381834 82551111
1319 5 78381834 80345337 1363 5 78381834 82552090
1320 5 78381834 80389787 1364 5 78381834 82555641
1321 5 78381834 80411639 1365 5 78381834 82555670
1322 5 78381834 80446855 1366 5 78381834 82556511
1323 5 78381834 80492790 1367 5 78381834 82559047
1324 5 78381834 80670554 1368 5 78381834 82561535
1325 5 78381834 80674679 1369 5 78381834 82610100
1326 5 78381834 80720509 1370 5 78381834 82676822
1327 5 78381834 80800856 1371 5 78381834 82676901
1328 5 78381834 80804587 1372 5 78381834 82883691
1329 5 78381834 80807409 1373 5 78381834 82954942
1330 5 78381834 80835734 1374 5 78381834 82971688
125
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PCT/US2015/016877
Table 1 (cont'cL)
Chromosomal Chromosomal
Segment Chr. Boundaryl Boundary2 Segment Cho. Bounclaryl Boundmy2
1375 5 78381834 83023965 1419 5 78381834
84936493
1376 5 78381834 83094205 1420 5 78381834
84943705
1377 5 78381834 83146355 1421 5 78381834
169454950
1378 5 78381834 83280630 1422 5 78381834
181522829
1379 5 78381834 83281412 1423 5 78381834
204759879
1380 5 78381834 83400242 1424 5 78381834
209874191
1381 5 78381834 83405797 1425 5 78519893
78520683
1382 5 78381834 83437132 1426 5 78519893
78765635
1383 5 78381834 83522252 1427 5 78519893
78780292
1384 5 78381834 83560095 1428 5 78519893
78813114
1385 5 78381834 83560204 1429 5 78519893
78814710
1386 5 78381834 83572400 1430 5 78519893
78814976
1387 5 78381834 83607661 1431 5 78519893
78815306
1388 5 78381834 83745342 1432 5 78519893
78821393
1389 5 78381834 83861275 1433 5 78519893
78826528
1390 5 78381834 83861633 1434 5 78519893
78826538
1391 5 78381834 83865653 1435 5 78519893
78826612
1392 5 78381834 83865914 1436 5 78519893
78918620
1393 5 78381834 83865920 1437 5 78519893
78918850
1394 5 78381834 83868010 1438 5 78519893
79056960
1395 5 78381834 84019752 1439 5 78519893
79163631
1396 5 78381834 84065912 1440 5 78519893
79176557
1397 5 78381834 84086632 1441 5 78519893
79188028
1398 5 78381834 84089603 1442 5 78519893
79201760
1399 5 78381834 84104814 1443 5 78519893
79230005
1400 5 78381834 84105175 1444 5 78519893
79230318
1401 5 78381834 84251635 1445 5 78519893
79505592
1402 5 78381834 84252180 1446 5 78519893
79510072
1403 5 78381834 84253030 1447 5 78519893
79538012
1404 5 78381834 84254208 1448 5 78519893
79538048
1405 5 78381834 84314930 1449 5 78519893
79538367
1406 5 78381834 84340523 1450 5 78519893
79669824
1407 5 78381834 84516340 1451 5 78519893
79682242
1408 5 78381834 84706916 1452 5 78519893
79699261
1409 5 78381834 84799488 1453 5 78519893
79710673
1410 5 78381834 84801081 1454 5 78519893
79861902
1411 5 78381834 84824103 1455 5 78519893
79867710
1412 5 78381834 84824203 1456 5 78519893
79867868
1413 5 78381834 84824816 1457 5 78519893
79867873
1414 5 78381834 84825422 1458 5 78519893
79961961
1415 5 78381834 84825763 1459 5 78519893
80086268
1416 5 78381834 84825942 1460 5 78519893
80190673
1417 5 78381834 84843411 1461 5 78519893
80190777
1418 5 78381834 84936441 1462 5 78519893
80192546
126
CA 02 9 3 958 0 2 0 16-013-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundaryl Boundary2 Segment Or. Boundaryl
Boundary 2
1463 5 78519893 80195395 1507 5 78519893
82431853
1464 5 78519893 80199923 1508 5 78519893
82446714
1465 5 78519893 80241911 1509 5 78519893
82446794
1466 5 78519193 80282785 1510 5 78519893
82551111
1467 5 78519893 80345337 1511 5 78519893
82552090
1468 5 78519893 80389787 1512 5 78519893
82555641
1469 5 78519893 80411639 1513 5 78519893
82555670
1470 5 78519893 80446855 1514 5 78519893
82556511
1471 5 78519893 80492790 1515 5 78519893
82559017
1472 5 78519893 80670554 1516 5 78519893
82561535
1473 5 78519893 80674679 1517 5 78519893
82610100
1474 5 78519893 80720509 1518 5 78519893
82676822
1475 5 78519893 80800856 1519 5 78519893
82676901
1476 5 78519893 80804587 1520 5 78519893
82883691
1477 5 78519893 80807409 1521 5 78519893
82954942
1478 5 78519893 80835734 1522 5 78519893
82971688
1479 5 78519893 80971764 1523 5 78519893
43023965
1480 5 78519893 60972258 1524 5 78519893
83094205
1481 5 78519893 80974450 1525 5 78519893
83146355
1482 5 78519893 81047638 1526 5 78519893
83280630
1483 5 78519893 81082921 1527 5 78519893
83281412
1484 5 78519893 81157909 1528 5 78519893
83400242
1485 5 78519893 81265937 1529 5 78519893
83405797
1446 5 78519893 81265937 1530 5 78519893
83437132
1487 5 78519893 81267485 1531 5 78519893
83522252
1488 5 78519893 81267499 1532 5 78519893
83560095
1489 5 78519893 81274512 1533 5 78519893
83560204
1490 5 78519893 81763618 1534 5 78519893
83572400
1491 5 78519893 81797217 1535 5 78519893
83607661
1492 5 78519893 81800186 1536 5 78519693
83745342
1493 5 78519893 81806213 1537 5 78519893
83861275
1494 5 78519893 81854583 1538 5 78519893
83861633
1495 5 78519893 81859374 1539 5 78519893
63865653
1496 5 78519893 81861368 1540 5 78519893
83865914
1497 5 78519893 81863686 1541 5 78519893
83865920
1498 5 78519893 81916850 1542 5 78519893
83868010
1499 5 78519893 81954891 1543 5 78519893
84019752
1500 5 78519893 81985250 . 1544 5 78519893
84065912
1501 5 78519893 82083752 1545 5 78519893
84086632
1502 5 78519893 82101253 1546 5 78519893
84089603
1503 5 78519893 82143124 1547 5 78519893
84104814
1504 5 78519893 82236318 1548 5 78519893
84105175
1505 5 78519893 82325587 1549 5 78519893
84251635
1506 5 78519893 12427210 1550 5 78519893
84252180
127
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'Fable 1 (cont'd.)
Chromosomal Chrmnomnal
Segment CM. Boundmy1 Boundmy2 Segment Cite. Boundaryl Boundary2
1551 5 78519893 84253030 1595 5 78758856
79538048
1552 5 78519893 84254208 1596 5 78758856
79538367
1553 5 78519893 84314930 1597 5 78758856
79669824
1554 5 78519893 84340523 1598 5 78758856
79682242
1555 5 78519893 84516340 1599 5 78758856
79699261
1556 5 78519893 84706916 1600 5 78758856
79710673
1557 5 78519893 84799488 1601 5 78758856
79861902
1558 5 78519893 84801081 1602 5 78758856
79867710
1559 5 78519893 84824103 1603 5 78758856
79867868
1560 5 78519893 84824203 1604 5 78758856
79867873
1561 5 78519893 84824816 1605 5 78758856
79.961961
1562 5 78519893 84825422 1606 5 78758856
80086268
1563 5 78519893 84825763 1607 5 78758856
80190673
1564 5 78519893 84825942 1608 5 78758856
80190777
1565 5 78519893 84843411 1609 5 78758856
80192546
1566 5 78519893 84936441 1610 5 78758856
80195395
1567 5 78519893 84936493 1611 5 78758856
80199923
1568 5 78519893 84943705 1612 5 78758856
80241911
1569 5 78519893 169454950 1613 5 78758856
80282785
1570 5 78519893 181522829 1614 5 78758856
80345337
1571 5 78519893 204759879 1615 5 78758856
80389787
1572 5 78519893 209874191 1616 5 78758856
80411639
1573 5 78758856 78765635 1617 5 78758856
80446855
1574 5 78758856 78780292 1618 5 78758856
80492790
1575 5 78758856 78813114 1619 5 78758856
80670554
1576 5 78758856 78814710 1620 5 78758856
80674679
1577 5 78758856 78814976 1621 5 78758856
80720509
1578 5 78758856 78815306 1622 5 78758856
80800856
1579 5 78758856 78821393 1623 5 78758856
80804587
1580 5 78758856 76826528 1624 5 78758356
80807409
1581 5 78758856 78826538 1625 5 78758856
80835734
,
1582 5 78758856 78826612 1626 5 78758856
80971764
1583 5 78758856 78918620 1627 5 78758856
80972258
1584 5 78758856 78918850 1628 5 78758856
80974450
1585 5 78758856 79056960 1629 5 78758856
81047638
1586 5 78758856 79163631 1630 5 78758856
81082921
1587 5 78758856 79176557 1631 5 78758856
81157909
1588 5 78758856 79188028 1632 5 78758856
81265937
1589 5 78758856 79201760 1633 5 78758856
81265937
1590 5 78758856 79230005 1634 5 78758856
81267485
1591 5 78758856 79230318 1635 5 78758856
81267499
1592 5 78758856 79505592 1636 5 78758856
81274512
1593 5 78758856 79510072 1637 5 78758856
81763618
1594 5 78758856 79538012 1638 5 78758856
81797217
,
128
CA 02939580 2016-08-11
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PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosmnal
Segment Chr. Boandmy1 Boundary 2 . Segment OIL Boundary1
Boundary2
1639 5 78758856 81800186 1683 5 78758856 83745342
1640 5 78758856 81806213 1684 5 78758856 83861275
1641 5 78758856 81854583 1685 5 78758856 83861633
1642 5 78758856 81859374 1686 5 78758856 83865653
1643 5 78758856 81861368 1687 5 78758856 83865914
1644 5 78758856 81863686 1688 5 78758856 83865920
1645 5 78758656 81916850 1689 5 78758856 83868010
1646 5 78758856 81954891 . 1690 5 78758856 84019752
1647 5 78758856 81985250 1691 5 78758856 84065912
1648 5 78758856 82083752 1692 5 78758856 84086632
1649 5 78758856 82101253 1693 5 78758856 84089603
1650 5 78758856 82143124 1694 5 78758856 84104814
1651 5 78758856 82236318 1695 5 78758856 84105175
1652 5 78758856 82325587 1696 5 78758856 84251635
1653 5 78758856 82427210 1697 5 78758856 84252180
1654 5 78758856 82431853 1698 5 78758856 84253030
1655 5 78758856 82446714 1699 5 78758056 84254208
1656 5 78758856 82446794 1700 5 78758856 84314930
1657 5 78758856 82551111 1701 5 78758856 84340523
1658 5 78758856 82552090 1702 5 78758856 84516340
1659 5 78758856 82555641 1703 5 78758856 84706916
1660 5 78758856 82555670 1704 5 78758856 84799488
1661 5 78758856 82556511 1705 5 78758856 84801081
1662 5 78758856 82559047 1706 5 78758856 84824103
1663 5 78758856 82561535 1707 5 78758856 84824203
1664 5 78758856 82610100 1708 5 78758856 84824816
1665 5 78758856 82676822 1709 5 78758856 84825422
1666 5 78758856 82676901 1710 5 78758856 84825763
1667 5 78758856 82883691 1711 5 78758856 84825942
1668 5 78758856 82954942 1712 5 78758856 84843411
1669 5 78758856 82971688 1713 5 78758656 84936441
1670 5 78758856 83023965 1714 5 78758856 64936493
1671 5 78758856 83094205 1715 5 78758856 84943705
1672 5 78758856 83146355 1716 5 78758856 169454950
1673 5 78758856 83280630 1717 5 78758856 181522829
1674 5 78758856 83281412 1718 5 78758856 204759879
1675 5 78758856 83400242 1719 5 78758856 209874191
1676 5 78758856 83405797 1720 5 78772058 78780292
1677 5 78758856 83437132 1721 5 78772058 78813114
1678 5 78758856 83522252 1722 5 78772058 78814710
1679 5 78758856 83560095 1723 5 78772058 78814976
1680 5 78758856 83560204 1724 5 78772058 78815306
1681 5 78758856 83572400 1725 5 78772058 78821393
1682 5 78758856 83607661 1726 5 78772058 78826528
129
CA 02 93 9580 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment CM. Boundary 1
Boundary 2
1727 5 78772058 78826538 1771 5 78772058 80835734
1728 5 78772058 78826612 1772 5 78772058 80971764
1729 5 78772058 78918620 1773 5 78772058 80972258
1730 5 78772058 78918850 1774 5 78772058 80974450
1711 5 78772058 79056960 1775 5 78772058 81047638
1732 5 78772058 79163631 1776 5 78772058 81082921
1733 5 78772058 79176557 1777 5 78772058 81157909
1734 5 78772058 79188028 1778 5 78772058 81265937
1735 5 78772058 79201760 1779 5 78772058 81265937
1736 5 78772058 79230005 , 1780 5 78772058 81267485
1737 5 78772058 79230318 1781 5 78772058 81267499
1738 5 78772058 79505592 1782 5 78772056 81274512
1739 5 78772058 79510072 1783 5 78772058 81763618
1740 5 78772058 79538012 1784 5 78772058 81797217
1741 5 78772058 79538048 1785 5 70772058 81800186
1742 5 78772058 79538367 1786 5 78772058 81806213
1743 5 78772058 79669824 1787 5 78772058 81854583
1744 5 78772058 79682242 1788 5 78772058 81859374
1745 5 78772058 79699261 1789 5 78772058 81861368
1746 5 78772058 79710673 1790 5 78772058 81863686
1747 5 78772058 79861902 1791 5 78772058 81916850
1748 5 78772058 79867710 1792 5 78772058 81954891
1749 5 78772058 79867868 1793 5 78772058 81985250
1750 5 78772058 79867873 1794 5 78772058 82083752
1751 5 78772058 79961961 1795 5 78772058 82101253
1752 5 78772058 80086268 1796 5 78772058 82143124
1753 5 78772058 80190673 1797 5 78772058 82236318
1754 5 78772058 80190777 1798 5 78772058 82325587
1755 5 78772058 80192546 1799 5 78772058 82427210
1756 5 78772058 80195395 1800 . 5 78772058 82431853
1757 5 78772058 80199923 1801 5 78772058 82446714
1758 5 78772058 80241911 1802 5 78772058 82446794
1759 5 78772050 80282785 1803 5 78772058 82551111
1760 5 78772058 80345337 1804 5 78772058 82552090
1761 5 78772058 80389787 1805 5 78772058 82555641
1762 5 78772058 80411639 1806 5 78772058 82555670
1763 5 78772058 80446855 1807 5 78772058 82556511
1764 5 78772058 80492790 1808 5 78772058 82559047
1765 5 78772058 80670554 1809 5 78772058 82561535
1766 5 78772058 80674679 1810 5 78772058 82610100
1767 5 78772058 80720509 1811 5 78772058 82676822
1768 5 78772058 80800856 1812 5 78772058 82676901
1769 5 78772058 80804587 1813 5 78772058 82883691
1770 5 78772058 80807409 1814 5 78772058 82954942
130
CA 02 9 3 95 8 0 2 016 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chnunclornal Chnunosornal
Svnara CIa Bounottuy1 Boundary 2 Segment Chn Boundary!
Boundary2
1815 5 78772058 82971688 1859 5 78772058 84936441
1816 5 78772058 83023965 1860 5 78772058 84936493
1817 5 78772058 83094205 1861 5 78772058 84943705
1818 5 78772058 83146355 1862 5 78772058 169454950
1819 5 78772058 83280630 1863 5 78772058 181522829
1820 5 78772058 83281412 1864 5 78772058 204759879
1821 5 78772058 83400242 1865 5 78772058 209874191
1822 5 78772058 83405797 1866 5 78804756 78813114
1823 5 78772058 83437132 1867 5 78804756 78814710
1824 5 78772058 83522252 1868 5 78804756 78814976
1825 5 78772058 83560095 1869 5 78804756 78815306
1826 5 78772058 83560204 1870 5 78804756 78821393
1827 5 78772058 13572400 1871 5 78804756 78826528
1828 5 78772058 83607661 1872 5 78804756 78826538
1829 5 78772058 83745342 1873 5 78804756 78826612
1830 5 78772058 83861275 1874 5 78804756 78918620
1831 5 78772058 83861633 1875 5 78804756 78918850
1832 5 78772058 63865653 1876 5 78804756 79056960
1833 5 78772058 83865914 1877 5 78804756 79163631
1834 5 78772058 83865920 1878 5 71804756 79176557
1835 5 78772058 83868010 1879 5 76804756 79188028
1836 5 78772058 84019752 1880 5 78804756 79201760
1837 5 78772058 84065912 1881 5 78804756 79230005
1838 5 78772058 84086632 1882 5 78804756 79230318
1839 5 78772058 84089603 1883 5 78804756 79505592
1840 5 78772058 84104814 1884 5 78804756 79510072
1841 5 78772058 84105175 1885 5 78804756 79538012
1842 5 78772058 84251635 1886 5 78804756 79538048
1843 5 78772058 84252180 1887 5 78804756 79538367
1844 5 78772058 84253030 1888 5 78804756 79669824
1845 5 78772058 84254208 1889 5 78604756 79682242
1846 5 78772058 84314930 1890 5 78804756 79699261
1847 5 78772058 84340523 1891 5 78804756 79710673
1848 5 78772058 84516340 1892 5 78804756 79861902
1840 5 78772058 84706916 1893 5 78804756 79867710
1850 5 78772058 84799488 1894 5 78804756 79867868
1851 5 78772058 84801081 1895 5 78804756 79867873
1852 5 78772058 84824103 1896 5 78804756 79961961
1853 5 78772058 84824203 1897 5 78804756 80086268
1854 5 78772058 84824816 1898 5 78804756 80190673
1855 5 78772058 84825422 1899 5 78804756 80190777
1856 5 78772058 84825763 1900 5 78804756 80192546
1857 5 78772058 84825942 1901 5 78804756 80195395
1858 5 78772058 84843411 1902 5 78604756 80199923
131
CA 02 939580 2 0 16-08-11
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PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Cho. Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
1903 5 78804756 80241911 1947 5 78804756 82446794
1904 5 78804756 80282785 1948 5 78804756 82551111
1905 5 78804756 80345337 1949 5 78804756 82552090
1906 5 78804756 80389787 1950 5 78804756 82555641
1907 5 78804756 80411639 1951 5 78804756 82555670
1908 5 78804756 80446855 1952 5 78804756 82556511
1909 5 78804756 80492790 1953 5 78804756 82559047
1910 5 78804756 80670554 1954 5 78804756 82561535
1911 5 78804756 80674679 1955 5 78804756 82610100
1912 5 78804756 80720509 1956 5 78804756 82676822
1913 5 78804756 80800856 1957 5 78804756 82676901
1914 5 78804756 80804587 1958 5 78804756 82883691
1915 5 78804756 80807409 1959 5 78804756 82954942
1916 5 78804756 80835734 1960 5 78804756 82971688
1917 5 78804756 80971764 1961 5 78804756 83023965
1918 5 78804756 80972258 1962 5 78804756 83094205
1919 5 78804756 80974450 1963 5 78804756 83146355
1920 5 78804756 81047638 1964 5 78804756 83280630
1921 5 78804756 81082921 1965 5 78804756 83281412
1922 5 78804756 81157909 1966 5 78804756 83400242
1923 5 78804756 81265937 1967 5 78804756 83405797
1924 5 78804756 81265937 1968 5 78804756 83437132
1925 5 78804756 81267485 1969 5 78304756 83522252
1926 5 78804756 81267499 1970 5 78804756 83560095
1927 5 78804756 81274512 1971 5 78804756 83560204
192..8 5 78804756 81763618 1972 5 78804756 83572400
1929 5 78804756 81797217 1973 5 78804756 83607661
1930 5 78804756 81800186 1974 5 78004756 83745342
1931 5 78804756 81806213 1975 5 78804756 83861275
1932 5 78804756 81854583 1976 5 78804756 83861633
1933 5 78804756 81859374 1977 5 78804756 83865653
1934 5 78804756 81861368 1978 5 78804756 83865914
1935 5 78804756 81863686 ' 1979 5 78804756 83865920
1936 5 78804756 81916850 1980 5 78804756 83868010
1937 5 78804756 81954891 1981 5 78804756 84019752
1938 5 78804756 81985250 1982 5 78804756 84065912
1939 5 78804756 82083752 1983 5 78804756 84086632
1940 5 78804756 82101253 1984 5 78804756 84089603
1941 5 78804756 82143124 1985 5 78804756 84104814
1942 5 78804756 82236318 1986 5 78804756 84105175
1943 5 78804756 82325587 1987 5 78804756 84251635
1944 5 78804756 82427210 1988 5 78804756 84252180
1945 5 78804756 82431853 1989 5 78804756 84253030
1946 5 78804756 82446714 1990 5 78804756 84254208
132
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'cl,)
CW-otrysontal Chumnommual
Segment Chr. Boundary 1 Boundary 2 Segment Chr. Boundary1
Boundmy2
1991 5 78804756 84314930 2035 5 78805059
79699261
1992 5 78804756 84340523 2036 5 78805059
79710673
1993 5 78804756 84516340 2037 5 78805059
79861902
1994 5 78804756 84706916 2038 5 78805059
79867710
1995 5 78804756 84799488 2039 5 78805059
79867868
1996 5 78804756 84801081 2040 5 78005059
79867873
1997 5 78804756 84824103 2041 5 78805059
79961961
1998 5 78804756 84824203 2042 5 78805059
80086268
1999 5 78804756 84824816 2043 5 78805059
80190673
2000 5 78804756 84825422 2044 5 78805059
80190777
2001 5 78804756 84825763 2045 5 78805059
80192546
2002 5 78804756 84825942 2046 5 78805059
80195395
2003 5 78004756 84843411 2047 5 78805059
80199923
2004 5 78804756 84936441 2048 5 78805059
80241911
2005 5 78804756 84936493 2049 5 78805059
80282785
2006 5 78804756 84943705 2050 5 78805059
80345337
2007 5 78804756 169454950 2051 5 78805059
80389787
2008 5 78804756 181522829 2052 5 78805059
80411639
2009 5 78804756 204759879 2053 5 78805059
80446855
2010 5 78804756 209874191 2054 5 78805059
80492790
2011 5 78805059 78813114 2055 5 78805059
80670554
2012 5 78805059 78814710 2056 5 78805059
80674679
2013 5 78805059 78814976 2057 5 78805059
80720509
2014 5 78805059 78815306 2058 5 78805059
80800856
2015 5 78805059 78821393 2059 5 78805059
80604587
2016 5 78805059 78826528 2060 5 78805059
80807409
2017 .5 78805059 78826538 2061 5 78805059
80835734
2018 5 78805059 78826612 2062 5 78805059
80971764
2019 5 78805059 78918620 2063 5 78805059
80972258
2020 5 78805059 78918850 2064 5 78805059
80974450
2021 5 78805059 79056960 2065 5 78805059
81047638
2022 5 78805059 79163631 2066 5 78805059
81082921
2023 5 78805059 79176557 2067 5 78805059
81157909
2024 5 78805059 79188028 2068 5 78805059
81265937
2025 5 78805059 79201760 2069 5 78805059
81265937
2026 5 78805059 79230005 2070 5 78805059
81267485
2027 5 78805059 79230318 2071 5 78805059
81267499
2028 5 78805059 79505592 2072 5 78805059
81274512
2029 5 78805059 79510072 2073 5 78805059
81763618
2030 5 78805059 79538012 2074 5 78805059
81797217
2031 5 78805059 79538048 2075 5 78805059
81800186
2032 5 78805059 79538367 2076 5 78805059
81806213
2033 5 78805059 79669824 2077 5 78805059
81854583
2034 5 76805059 79682242 2078 5 78805059
81859374
133
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
_
Table 1 (contd.)
Chromosomal Chromosomal
Segment Om Boundary 1 Bouodary2 Segment Chr. Bouodary1
Boundary 2
2079 5 78805059 81061368 2123 5 78805059
83865914
2080 5 78805059 81863686 2124 5 78805059
83865920
2081 5 78805059 81916850 2125 5 78805059
03868010
2082 5 78805059 81954891 2126 5 78805059
84019752
2083 5 78805059 81985250 2127 5 78805059
84065912
2084 5 78805059 82083752 2128 5 78805059
84086632
2085 5 76805059 82101253 2129 5 78805059
84089603
2086 5 78805059 82143124 2130 5 78805059
84104814
2087 5 78805059 82236318 2131 5 78805059
84105175
2088 5 78805059 82325587 2132 5 78805059
84251635
2089 5 78805059 82427210 2133 5 78805059
84252180
2090 5 78805059 82431853 2134 5 78805059
84253030
2091 5 78805059 82446714 2135 5 78805059
84254208
2092 5 78805059 82446794 2136 5 78805059
84314930
2093 5 78805059 82551111 2137 5 78805059
84340523
2094 5 78805059 02552090 2138 5 78805059
84516340
2095 5 78805059 82555641 2139 5 78805059
04706916
2096 5 78805059 82555670 2140 5 78805059
84799488
2097 5 78805059 82556511 2141 5 78805059
84801081
2098 5 78805059 82559047 2142 5 78805059
84824103
2099 5 78805059 82561535 2143 5 78805059
84824203
2100 5 78805059 82610100 2144 5 78805069
84824816
2101 5 78805059 82676822 2145 5 78805059
84825422
2102 5 78805059 82676901 2146 5 78805059
84825763
2103 5 78805059 82883691 2147 5 78805059
84825942
2104 5 78805059 82954942 2148 5 78805059
84843411
2105 5 78805059 82971688 2149 5 78805059
84936441
2106 5 78805059 83023965 2150 5 78805059
84936493
2107 5 78805059 83094205 ' 2151 5 78805059
84943705
2108 5 78805059 83146355 2152 5 78805059
169454950
2109 5 78805059 83280630 2153 5 78805059
181522829
2110 5 78805059 83281412 2154 5 78805059
204759879
2111 5 78805059 83400242 2155 5 76805059
209874191
2112 5 78805059 83405797 2156 5 78814424
78814710
2113 5 78805059 83437132 2157 5 78814424
78814976
2114 5 78805059 83522252 2158 5 78814424
78815306
2115 5 78805059 83560095 2159 5 78814424
78821393
2116 5 78805059 83560204 2160 5 78814424
78826528
2117 5 78805059 83572400 2161 5 78814424
71826538
2118 5 78805059 83607661 2162 5 78814424
78826612
2119 5 78805059 83745342 2163 5 78814424
78918620
2120 5 78835059 83861275 2164 5 78814424
78918850
2121 5 78805059 83061633 2165 5 78814424
79056960
2122 5 70805059 83865653 2166 5 78814424
79163631
134
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Cite. Boundary 1 Boundary2 Segment flu. Boundary1
Boundary2
2167 5 78814424 79176557 2211 5 78814424
81157909
2168 5 78814424 79188028 2212 5 78814424
81265937
2169 5 78814424 79201760 2213 5 78814424
81265937
2170 5 78814424 79230005 2214 5 78814424
81267485
2171 5 78814424 79230318 2215 5 78814424
81267499
2172 5 78814424 79505592 2216 5 78814424
81274512
2173 5 78814424 79510072 2217 5 78814424
81763618
2174 5 78814424 79538012 2218 5 78814424
81797217
2175 5 78814424 79538048 2219 5 78814424
81800186
2176 5 78814424 79538167 2220 5 78814424
81806213
2177 5 78814424 79669824 2221 5 78814424
81854583
2178 5 78814424 79682242 2222 5 78814424
81859374
2179 5 78814424 79699261 2223 5 78814424
81861368
2180 5 78814424 79710673 2224 5 78814424
81863686
2181 5 78814424 79861902 2225 5 78814424
81916850
2182 5 78814424 79867710 2226 5 78814424
81954891
2183 5 78814424 79867868 2227 5 78814424
81985250
2184 5 78814424 79867873 2228 5 78814424
82083752
2185 5 78814424 79961961 2229 5 78814424
82101253
2186 5 78814424 80086268 2230 5 78814424
82143124
2187 5 78814424 80190673 2231 5 78814424
82236318
2188 5 78814424 80190777 2232 5 78814424
82325587
2169 5 78814424 80192546 2233 5 78814424
82427210
2190 5 78814424 00195395 2234 5 78814424
82431853
2191 5 78814424 80199923 2235 5 78814424
82446714
2192 5 78814424 80241911 2236 5 78814124
82446794
2193 5 78814424 80282785 2237 5 78814424
82551111
2194 5 78814424 80345337 2238 5 78814424
82552090
2195 5 78814424 80389787 2239 5 78814424
82555641
2196 5 78814424 80411639 2240 5 78814424
82555670
2197 5 78814424 80446855 2241 5 78814424
02556511
2198 5 78814424 80492790 2242 5 78814124
82559047
2199 5 78814424 80670554 2243 5 76814424
82561535
2200 5 78814424 80674679 2244 5 78814424
82610100
2201 5 78814424 80720509 2245 5 78814424
82676822
2202 5 78814424 80800856 2246 5 78814424
82676901
2203 5 78814424 80804587 2247 5 78814424
82883691
2204 5 78814424 80807409 2248 5 78814124
82954942
2205 5 78814424 80835734 2249 5 78814424
82971688
2206 5 78814424 80971764 2250 5 78814424
83023965
2207 5 78814424 80972258 2251 5 78814424
83094205
2208 5 78814424 80974450 2252 5 78814424
83146355
2209 5 78814424 81047638 2253 5 78814424
83280630
2210 5 78814424 81082921 2254 5 78814424
83281412
135
CA 0 2 9 3 95 8 0 2 0 1 6 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundary1 flowldary2 Segment Chr. Boundary1 Famodary2
2255 5 78814424 83400242 2299 5 78814424
209874191
2256 5 78814424 83405797 2300 5 78819803
78821393
2257 5 78814424 83437132 2301 5 78819803
78826528
2258 5 78814424 83522252 2302 5 78819803
78826538
2259 5 78814424 83560095 2303 5 78819803
78826612
2260 5 78814424 83560204 2304 5 78819803
78918620
2261 5 78814424 83572400 2305 5 78819803
76918850
2262 5 78814424 83607661 2306 5 78819803
79056960
2263 5 78814424 83745342 2307 5 70819803
79163631
2264 5 78814424 83861275 2308 5 78819803
79176557
2265 5 78814424 83861633 2309 5 78819803
79188028
2266 5 78814424 83865653 2310 5 78819803
79201760
2267 5 78814424 83865914 2311 5 78819803
79230005
2268 5 78814424 83865920 2312 5 78819803
79230318
2269 5 78814424 83868010 2113 5 78819803
79505592
2270 5 78814424 84019752 2314 5 78819803
79510072
2271 5 78814424 84065912 2315 5 78819803
79938012
2272 5 78814424 84086632 2316 5 78819803
79538048
2273 5 78814424 84089603 2317 5 78819803
79538367
2274 5 78814424 84104814 2318 5 78819803
79669824
2275 5 78814424 84105175 2319 5 78819803
79682242
2276 5 78814424 84251635 2320 5 78819803
79699261
2277 5 78814424 84252180 2321 5 76819803
79710673
2278 5 78814424 84253030 2322 5 78819803
79861902
2279 5 78814424 84254208 2323 5 78819803
79867710
2280 5 7E814424 84314930 2324 5 78819803
79867868
2281 5 78814424 84340523 2325 5 78819803
79867873
2282 5 78814424 84516340 2326 5 78819803
79961961
2283 5 78814424 84706916 2327 5 78819803
80086268
2284 5 78814424 84799488 2328 5 78819803
80190673
2285 5 78814424 84801081 2329 5 78819803
80190777
2286 5 78814424 84824103 2330 5 78819803
80192546
2287 5 78814424 84824203 2331 5 78819803
80195395
2288 5 78814424 84824816 2332 5 78819603
80199923
2289 5 78814424 84825422 2333 5 78819803
80241911
2290 5 78814424 84825763 2334 5 78819803
80282785
2291 5 78814424 84825942 2335 5 78819803
80345337
2292 5 78814424 84843411 2336 5 78819803
80389787
2293 5 78814424 84936441 2337 5 78819803
80411639
2294 5 78814424 84936493 2338 5 78819803
80446855
2295 5 78814424 84943705 2339 5 78819803
80492790
2296 5 78814424 169454950 2340 5 78819803
80670554
2297 5 78814424 181522829 2341 5 78819803
80674679
2298 5 78814424 204759879 2342 5 78819803 80720509
136
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (conticl.)
Cluomemomal Chromosomal
Segment CM. Boundaryl Boundary2 Sughlont Gm Bdundani1 Boundury2
2343 5 78819803 80800856 2387 5 78819803 82676901
2344 5 78819803 80804587 2388 5 78819803 82883691
2345 5 78819803 80807409 2389 5 78819803 82954942
2346 5 78819803 80835734 2390 5 78819803 82971688
2347 5 70819803 80971764 2391 5 78819803 83023965
2348 5 78819803 80972258 2392 5 78819803 83094205
2349 5 78819803 80974450 2393 5 78819803 83146355
2350 5 78819803 81047638 2394 5 78819803 83280630
2351 5 78819803 81082921 2395 5 78819803 83281412
2352 5 78819803 81157909 2396 5 78819803 83400242
2353 5 78819803 81265937 2397 5 78819803 83405797
2354 5 78819803 81265937 2398 5 78819803 83437132
2355 5 78819803 81267485 2399 5 78819803 83522252
2356 5 78819803 81267499 2400 5 78819803 83560095
2357 5 78819803 81274512 2401 5 78819803 83560204
2358 5 78819803 81763618 2402 5 78819803 83572400
2359 5 78819803 81797217 2403 5 78819803 83607661
2360 5 78819803 81800186 2404 5 78819803 83745342
2361 5 78819803 81806213 2405 5 78819803 83061275
2362 5 78819803 81854583 2406 5 78819803 83861633
2363 5 78819803 81859374 2407 5 78819803 83865653
2364 5 78819803 81861368 2408 5 78819803 83865914
2365 5 78819803 81863686 2409 5 78819803 83865920
2366 5 78819803 81916850 2410 5 78819803 83868010
2367 5 78819803 81954891 2411 5 78819803 84019752
2368 5 78819803 81986250 2412 5 78819803 84065912
2369 5 78819803 82083752 2413 5 78819803 84086632
2370 5 78819803 82101253 2414 5 78819803 84089603
2371 5 78819803 82143124 2415 5 78819803 84104814
2372 5 78819803 82236318 2416 5 78819803 84105175
2373 5 78819803 82325587 2417 5 78819801 84251635
2374 5 78819803 82427210 2418 5 78819803 84252180
2375 5 76819803 52431853 2419 5 78819803 84253030
2376 5 78819803 82446714 2420 5 78819803 84254208
2377 5 78819803 82446794 2421 5 78819803 84314930
2378 5 78819803 82551111 2422 5 78819803 84340523
2379 5 78819803 82552090 2423 5 78819803 84516340
2380 5 78819803 82555641 2424 5 78819803 84706916
2381 5 78819803 82555670 2425 5 78819803 84799488
2382 5 78819803 82556511 2426 5 78819803 84801081
2383 5 78819803 82559047 2427 5 78819803 84824103
2384 5 78819803 82561535 2428 5 78819803 84824203
2385 5 78819803 82610100 2429 5 78819803 84824816
2386 5 78819801 82676822 2430 5 78819803 84825422
137
CA 02 9 3 95 8 0 2 0 16 ¨ 0 13 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment CAL Boundary1 Boundary2 Segment Chlt Boundary 1
Boundary2
2431 5 78819803 84825763 2475 5 78820119 80282785
2432 5 78819803 84825942 2476 5 78820119 80345337
2433 5 78819803 84843411 2477 5 78820119 80389787
2434 5 78819803 84936441 2478 5 78820119 80411639
2435 5 78819803 84936493 2479 5 78820119 80446855
2436 5 78819803 84943705 2480 5 78820119 80492790
2437 5 78819803 169454950 2481 5 78820119 80670554
2438 5 78819803 181522829 ' 2482 5 78820119
80674679
2439 5 78819803 204759879 2483 5 78820119 80720509
2440 5 78819803 209874191 2484 5 78820119 80800856
2441 5 78820119 78821393 2485 5 78820119 80804587
2442 5 78820119 78826528 2486 5 78820119 80807409
2443 5 78820119 78826538 2487 5 78820119 80835734
2444 5 78820119 78826612 2488 5 78820119 80971764
2445 5 78820119 78918620 2489 5 78820119 80972258
2446 5 78820119 78918855 2490 5 78820119 80974450
2447 5 78820119 79056960 2491 5 78820119 81047638
2448 5 78820119 79163631 2492 5 78820119 81082921
2449 5 78820119 79176557 2493 5 78820119 81157909
2450 5 78820119 79188028 2494 5 78820119 81265937
2451 5 78820119 79201760 2495 5 78820119 81265937
2452 5 78820119 79230005 2496 5 78820119 81267485
2453 5 78820119 79230318 2497 5 78820119 81267499
2451 5 78820119 79505592 2498 5 78820119 81274512
2455 5 78820119 79510072 2499 5 78820119 81763618
2456 5 78820119 79538012 2500 5 78820119 81797217
2457 5 78820119 79538048 2501 5 78820119 81800186
2458 5 78820119 79538367 2502 5 78820119 81806213
2459 5 78820119 79669824 2503 5 78820119 81854583
2460 5 78820119 79682242 2504 5 78820119 81859374
2461 5 78820119 79699261 2505 5 78820119 81861368
2462 5 78820119 79710673 2506 5 78820119 81863686
2463 5 78820119 79861902 2507 5 78820119 81916850
2464 5 78820119 79867710 2508 5 78820119 81954891
2465 5 78820119 79867868 2509 5 78820119 81985250
2466 5 78820119 79867873 2510 5 78820119 82083752
2467 5 78820119 79961961 2511 5 78820119 82101253
2468 5 78820119 110086268 2512 5 78820119 82143124
2469 5 78820119 80190673 2513 5 78820119 82236318
2470 5 78820119 80190777 2514 5 78820119 82325587
2471 5 78820119 80192546 2515 5 78820119 82427210
2472 5 78820119 80195395 2516 5 78820119 82431853
2473 5 78820119 80199923 2517 5 78820119 82446714
2474 5 78820119 80241911 2518 5 78820119 82446794
138
CA 02 9 3 95 8 0 2 016 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal ClurnnoannW
Segment Cbr Boundary 1 Boundary2 Segment .. Or. .. Boundary] ..
Boundany2
2519 5 78820119 82551111 2563 5 78820119 84340523
2520 5 76820119 82552090 2564 5 78820119 84516340
2521 5 78320119 82555641 2565 5 78820119 84706916
2522 5 78820119 82555670 2566 5 78820119 84799488
2523 5 78820119 82556511 2567 5 78820119 84801081
2524 5 78820119 82559047 2568 5 78820119 84824103
2525 5 78820119 82561535 2569 5 78820119 84824203
2526 5 78820119 82610100 2570 5 78820119 84824816
2527 5 78820119 82676822 2571 5 78820119 84825422
2528 5 78820119 82676901 2572 5 78820119 84825763
2529 5 78820119 82883691 2573 5 78820119 84825942
2530 5 78820119 82954942 2574 5 78820119 84843411
2531 5 78820119 82971686 2575 5 78820119 84936441
2532 5 78820119 83023965 2576 5 78820119 84936493
2533 5 78820119 83094205 2577 5 78820119 84943705
2534 5 78820119 83146355 2578 5 78820119 169454950
2535 5 78820119 83280630 2579 5 78820119 181522829
2536 5 78820119 83281412 2580 5 78820119 204759879
2537 5 78820119 83400242 2581 5 78820119 209874191
2538 5 78820119 83405797 2582 5 78904639 78918620
2539 5 78820119 83437132 2583 5 78904639 78918850
2540 5 78820119 83522252 2584 5 78904639 79056960
2541 5 78820119 83560095 2585 5 78904639 79163631
, 2542 5 78820119 83560204 2586 5 78901639 79176557
2543 5 78820119 83572400 2587 5 78904639 79188028
2544 5 78820119 83607661 2588 5 78904639 79201760
2545 5 78820119 83745342 2589 5 78904639 79230005
2546 5 78820119 83861275 2590 5 78904639 79230318
2547 5 78820119 83861633 2591 5 78904639 79505592
2548 5 78820119 83865653 2592 5 78904639 79510072
2549 5 78820119 83865914 2593 5 78904639 79536012
2550 5 78820119 83865920 2594 5 78904639 79538048
2551 5 78820119 83868010 2595 5 78904639 79538367
2552 5 78820119 84019752 2596 5 78904639 79669824
2553 5 78820119 84065912 2597 5 78904639 79682242
2554 5 78820119 84086632 2598 5 78904639 79699261
2555 5 78820119 84089603 2599 5 78904639 79710673
2556 5 78820119 84104814 2600 5 78904639 79861902
2557 5 78820119 - 84105175 2601 5 78904639 79867710
2558 5 78820119 84251635 2602 5 78904639 79867868
2559 5 78820119 84252180 2603 5 78904639 79867873
2560 5 78820119 84253030 2604 5 78904639 79961961
2561 5 78820119 84254208 2605 5 78904639 80086268
2562 5 78820119 84314930 2606 5 78904639 80190673
139
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr, Boundary 1 Boundary 2 Segment Clx. Boundary1
Boundary 2
2607 5 78904639 80190777 2651 5 78904639 82325587
2608 5 78904639 80192546 2652 5 78904639 82427210
2609 5 78904639 80195395 2653 5 78904639 82431853
2610 5 78904639 80199923 2654 5 78904639 82446714
2611 5 78904639 80241911 2655 5 78904639 82446794
2612 5 78904639 80282785 2656 5 78904639 82551111
2613 5 78904639 80345337 2657 5 78904639 82552090
2614 5 78904639 80389787 2658 5 78904639 82555641
2615 5 78904639 80411639 2659 5 78904639 82555670
2616 5 78904639 80446855 2660 5 78904639 82556511
2617 5 78904639 80492790 2661 5 78904639 82559047
2618 5 78904639 80670554 2662 5 78904639 82561535
2619 5 78904639 00674679 2663 5 78904639 82610100
2620 5 78904639 80720509 2664 5 78904639 82676822
2621 5 78904639 80800856 2665 5 78904639 82676901
2622 5 78904639 80804587 2666 5 78904639 82883691
2623 5 78904639 80807409 2667 5 78904639 82954942
2624 5 78904639 80835734 2668 5 78904639 82971688
2625 5 78904639 80971.764 2669 5 78904639 83023965
2626 5 78904639 80972258 2670 5 78904639 83094205
2627 5 78904639 80974450 2671 5 78904639 83146355
2628 5 78904639 81047638 2672 5 78904639 83280630
2629 5 78904639 81082921 2673 5 78904639 83281412
2630 5 78904639 81197909 2674 5 78904639 83400242
2631 5 78904639 81265937 2675 5 78904639 83405797
2632 5 78904639 81265937 2676 5 70904639 83437132
2633 5 78904639 81267485 2677 5 78904639 83522252
2634 5 78904639 81267499 2678 5 78904639 83560095
2635 5 78904639 81274512 2679 5 78904639 83560204
2636 5 78904639 81763618 2680 5 78904639 83572400
2637 5 78904639 81797217 2681 5 78904639 83607661
2638 5 78904639 81800186 2682 5 78904639 83745342
2639 5 78904639 81806213 2683 5 78904639 83861275
2640 5 78904639 81854583 2684 5 78904639 83861633
2641 5 78904639 81859374 2685 5 78904639 83865653
2642 5 78904639 81861368 2.586 5 78904639 83865914
2643 5 78904639 81863686 2687 5 78904639 83865920
2644 5 78904639 81916850 2688 5 78904639 83868010
2645 5 78904639 81954891 2689 5 78904639 84019752
2646 5 78904639 81985250 2690 5 78904639 84065912
2647 5 78904639 82083752 2691 5 78904639 84086632
2648 5 78904639 82101253 2692 5 78904639 84089603
2649 5 78904639 82143124 2693 5 78904639 84104814
2650 5 78904639 82236318 2694 5 78904639 84105175
140
CA 02 9 3 95 8 0 2 016 ¨ 08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Clr. Boundary1 Boundary2 Segment Clot. Boundary1 Boundary2
2695 5 78904639 84251635 2739 5 78918620
79867873
2696 5 78904639 84252180 2740 5 78918620
79961961
2697 5 78904639 84253030 2741 5 78918620
80086268
2698 5 78904639 84254208 2742 5 78918620
80190673
2699 5 78904639 84314930 2743 5 78918620
80190777
2700 5 78904639 84340523 2744 5 78918620
80192546
2701 5 78904639 84516340 2745 5 78918620
80195395
2702 5 78904639 84706916 2746 5 78918620
80199923
2703 5 78904639 84799488 2747 5 78918620
80241911
2704 5 78904639 84801081 2748 5 78918620
80282785
2705 5 78904639 84824103 2749 5 78918620
80345337
2706 5 78904639 84824203 2750 5 78918620
80389787
2707 5 78904639 84824816 2751 5 78918620
80411639
2708 5 78904639 84825422 2752 5 78918620
80446855
2709 5 78904639 84825763 2753 5 78918620
80492790
2710 5 78904639 84825942 2754 5 78918620
80670554
2711 5 78904639 84843411 2755 5 78918620
80674679
2712 5 78904639 84936441 2756 5 78918620
80720509
2713 5 78904639 84936493 2757 5 78918620
80800856
2714 5 78904639 84943705 2758 5 78918620
80804587
2715 5 78904639 169454950 2759 5 78918620
80807409
2716 5 78904639 181522829 2760 5 78918620
80835734
2717 5 78904639 264759879 2761 5 78918620
80971764
2718 5 78904639 209874191 2762 5 78918620
80972258
2719 5 78918620 78918850 2763 5 78918620
80974450
2720 5 78918620 79056960 2764 5 78918620
81047638
2721 5 78918620 79163631 2765 5 78918620
81082921
2722 5 78918620 79176557 2766 5 78918620
81157909
2723 5 78918620 79188028 2767 5 78918620
81265937
2724 5 78918620 79201760 2768 5 78918620
81265937
2725 5 78918620 79230005 2769 5 78918620
81267485
2726 5 78918620 79230318 2770 - 5 78918620
81267499
2727 5 78918620 79505592 2771 5 78918620
81274512
2728 5 78918620 79510072 2772 5 78918620
81763618
2729 5 78918620 79538012 2773 5 78918620
81797217
2730 5 78918620 79538048 2774 5 78918620
81800186
2731 5 78918620 79538367 2775 5 78918620
81806213
2732 5 78918620 79669824 2776 5 78918620
81854583
2733 5 78918620 79682242 2777 5 78918620
81859374
2734 5 78918620 79699261 2778 5 78918620
81861368
2735 5 78918620 79710673 2779 5 78918620
81863686
2736 5 78918620 79861902 2780 5 78918620
819161150
2737 5 78918620 79867710 2781 5 78918620
81954891
2738 5 78918620 79867868 2782 5 78918620
81985250
141
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Clu-, Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
2783 5 78918620 82083752 2827 5 78918620 84086632
2784 5 78918620 82101253 2828 5 78918620 84089603
2785 5 78918620 82143124 2829 5 78918620 84104814
2786 5 78918620 82236318 2830 5 78918620 84105175
2787 9 78918620 82325587 2831 5 78918620 84251635
2788 5 78918620 82427210 2832 5 78918620 84252180
2789 5 78918620 82431853 2833 5 78918620 84253030
2790 5 78918620 82446714 2834 5 78918620 84254208
2791 5 78918620 82446794 2835 5 78918620 84314930
2792 5 78918620 82551111 2836 5 78918620 84340523
2793 5 78918620 82552090 2837 5 78918620 84516340
2794 5 78918620 82555641 2838 5 78918620 84706916
2795 5 78918620 82555670 2839 5 78918620 84799488
2796 5 78918620 82556511 2840 5 78918620 84801081
2797 5 78918620 82559047 2841 5 78918620 84824103
2798 5 78918620 82561535 2842 5 78918620 84824203
2799 5 78918620 82610100 2843 5 78918620 84824816
2800 5 78918620 82676822 2844 5 78918620 84825422
2801 5 78918620 82676901 2845 _ 5 78918620 84825763
2802 5 78918620 82883691 2846 5 78918620 84825942
2803 5 78918620 82954942 2847 5 78918620 84843411
2804 5 78918620 82971688 2848 5 78918620 84936441
2805 5 78918620 83023965 2849 5 78918620 84936493
2806 5 78918620 83094205 2850 5 78918620 84943705
2807 5 78918620 83146355 2851 5 78918620 169454950
2808 5 78918620 83280630 2852 5 78918620 181522829
2809 5 78918620 83281412 2853 5 78918620 204759879
2810 5 78918620 83400242 2854 5 78918620 209874191
2811 5 78918620 83405797 2855 5 79055654 78918620
2812 5 78918620 83437132 2856 5 79055654 79056960
2813 5 78918620 83522252 2857 5 79055654 79163631
2814 5 78918620 83560095 2858 5 79055654 79176557
2815 5 789186211 83560204 2859 5 79055654 79188028
2816 5 78918620 83572400 2860 5 79055654 79201760
2817 5 78918620 83607661 2861 9 79055654 79230005
Mg 5 78918620 83745342 2862 5 79055654 79230318
2819 5 78918620 83861275 2863 5 79055654 79505592
2820 5 78918620 83861633 2864 5 79055654 79510072
2821 5 78918620 83865653 2865 5 79055654 79538012
2822 5 78918620 83865914 2866 5 79055654 79538046
2823 5 78918620 83865920 2867 5 79055654 79538367
2824 5 78918620 83868010 2868 5 79055654 79669824
2825 5 78918620 84019752 2869 5 79055654 79682242
2826 5 78918620 84069912 2870 5 79055654 79699261
142
CA 02 93 9580 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chrcanosomed ChrmnownnM
Segment CIT. Boundary 1 Boundary2 Segment ChT Boundary!
Boundary2
2871 5 79055654 79716673 2915 5 79055654
81863686
2872 5 79055654 79861902 2916 5 79055654
81916850
2873 5 79055654 79867710 2917 5 79055654
81954891
2874 5 79055654 79867868 2918 5 79055654
81985250
2875 5 79055654 79867873 2919 5 79055654
82083752
2876 5 79055654 79961961 2920 5 79055654
82101253
2877 5 79055654 80086268 2921 5 79055654
82143124
2878 5 79055654 80190673 2922 5 79055654
82236318
2879 5 79055654 80190777 2923 5 79055654
82325587
2880 5 79055654 80192546 2924 5 79055654
82427210
2881 5 79055654 80195395 2925 5 79055654
82431853
2882 5 79055654 80199923 2926 5 79055654
82446714
2883 5 79055654 80241911 2927 5 79055654
82446794
2884 5 79055654 80282785 2928 5 79055654
82551111
2885 5 79055654 80345337 2929 5 79055654
82552090
2886 5 79055654 80389787 2930 5 79055654
82555641
2887 5 79055654 80411639 2931 5 79055654
82555670
2888 5 79055654 80446855 2932 5 79055654
82556511
2889 5 79055654 80492790 2933 5 79055654
82559047
2890 5 79055654 80670554 2934 5 79055654
82561535
2891 5 79055654 60674679 2935 5 79055654
82610100
2892 5 79055654 80720509 2936 5 79055654
82676822
2893 5 79055654 80800856 2937 5 79055654
82676901
2894 5 79055654 80804587 2938 5 79055654
82883691
2895 5 79055654 80807409 2939 5 79055654
82954942
2896 5 79055654 80835734 2940 5 79055654
82971688
2897 5 79055654 80971764 2941 5 79055654
83023965
2898 5 79055654 80972258 2942 5 79055654
83094205
2899 5 79055654 80971450 2943 5 79055654
83146355
2900 5 79055654 81047638 2944 5 79055654
83280630
2901 5 79055654 81082921 2945 5 79055654
83281412
2902 5 79055654 81157909 2946 5 79055654
83400242
2903 5 79055654 81265937 2947 5 79055654 ,
83405797
2904 5 79055654 81265937 2948 5 79055654
83437132
2905 5 79055654 81267485 2949 5 79055654
83522252
2906 5 79055654 81267499 2950 5 79055654
83560095
2907 5 79055654 81274512 2951 5 79055654
83560204
2908 5 79055654 81763618 2952 5 79055654
83572400
2909 5 79055654 81797217 2953 5 79055654
83607661
2910 5 79055654 81800186 2954 5 79055654
83745342
2911 5 79055654 81806213 2955 5 79055654
83861275
2912 5 79055654 81854583 2956 5 79055654
83861633
2913 5 79055654 81859374 2957 5 79055654
83865653
2914 5 79055654 81861368 2958 5 79055654
83865914
143
CA 02 93 9580 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (eont'd.)
Chromosomal Chromosomal
Segment Cbr. Boundary 1 Boundary 2 Segment Chr. Boundary!
Boundary 2
2959 5 79055654 83865920 3003 5 79162381
79682242
2960 5 79055654 83868010 3004 5 79162381
79699261
2961 5 79055654 84019752 3005 5 79162381
79710673
2962 5 79055654 84065912 3006 5 79162381
79861902
2963 5 79055654 84086632 3007 5 79162381
79867710
2964 5 79055654 84089603 3008 5 79162381
79867868
2965 5 79055654 84104814 3009 5 79162381
79867873
2966 5 79055654 84105175 3010 5 79162381
79961961
2967 5 79055654 84251635 3011 5 79162381
80086268
2968 5 79055654 84252180 3012 5 79162381
80190673
2969 5 79055654 84253030 3013 5 79162381
80190777
2970 5 79055654 84254208 3014 5 79162381
80192546
2971 5 79055654 84314930 3015 5 79162381
80195395
2972 5 79055654 84340523 3016 5 79162381
80199923
2973 5 79055654 84516340 3017 5 79162381
802.41911
2974 5 79055654 84706916 3018 5 79162381
80282785
2975 5 79055654 84799488 3019 5 79162381
80345337
2976 5 79055654 84801081 3020 5 79162381
80389787
,
2977 5 79055654 84824103 3021 5 79162381
80411639
2978 5 79055654 84824203 3022 5 79162381
80446855
2979 5 79055654 84824816 3023 5 79162381
80492790
2980 5 79055654 84825422 3024 5 79162381
80670554
2981 5 79055654 84825763 3025 5 79162381
80674679
2982 5 79055654 84825942 3026 5 79162381
80720509
2983 5 79055654 84843411 3027 5 79162381
80800856
2984 5 79055654 84936441 3028 5 79162381
80804587
2985 5 79055654 84936493 3029 5 79162381
80807409
2986 5 79055654 84943705 3030 5 79162381
80835734
2987 5 79055654 169454950 3031 5 79162381
80971764
2988 5 79055654 181522829 3032 5 79162381
80972258
2989 5 79055654 204759879 3033 5 79162581
80974450
2990 5 79055654 209874191 3034 5 79162381
81047638
2991 5 79162381 79163631 3035 5 79162381
81082921
2992 5 79162381 79176557 3036 5 79162381
81157909
2993 5 79162381 79188028 3037 5 79162381
81265937
2994 5 79162381 79201760 3038 5 79162381
81265937
2995 5 79162381 79230005 3039 5 79162381
81267485
2996 5 79162381 79230318 3040 5 79162381
81267499
2997 5 79162381 79505592 3041 5 79162381
81274512
2998 5 79162381 79510072 3042 5 79162381
81763618
2999 5 79162381 79538012 3043 5 79162381
81797217
3000 5 79162381 79538048 3044 5 79162381
81800186
3001 5 79162381 79538367 3045 5 79162381
81806213
3002 5 79162381 79669824 3046 5 79162381
81854583
144
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundapyl Boundary2 Segment Clm Romuhuy1 15oundary2
3047 5 79162381 81859374 3091 5 79162381 83865653
3048 5 79162381 81861368 3092 5 79162381 83865914
3049 5 79162381 81863686 3093 5 79162381 83865920
3050 5 79162381 81916850 3094 5 79162381 83868010
3051 5 79162381 81954891 3095 5 79162381 84019752
3052 5 79162381 81985250 3096 5 79162381 84065912
3053 5 79162381 82083752 3097 5 79162381 84086632
3054 5 79162381 82101253 3098 5 79162381 84089603
3055 5 79162381 82143124 3099 5 79162381 84104814
3056 5 79162381 82236318 3100 5 79162381 84105175
3057 5 79162381 82325587 3101 5 79162381 84251635
3058 5 79162381 82427210 1102 5 79162381 84252180
3059 5 79162381 82431853 3103 5 79162381 84253030
3060 5 79162381 82446714 3104 5 79162381 84254208
3061 5 79162381 82446794 3105 5 79162381 84314930
3062 5 79162381 82551111 3106 5 79162381 84340523
3063 5 79162381 82552090 3107 5 79162381 84516340
3064 5 79162381 82555641 3108 5 79162381 84706916
3065 5 79162381 82555670 3109 5 79162381 14799488
3066 5 79162381 82556511 3110 5 79162381 84801081
3067 5 79162381 82559047 3111 5 79162381 84824103
3060 5 79162381 82561535 3112 5 79162381 84824203
3069 5 79162381 82610100 3113 5 79162381 84824816
3070 5 79162381 82676822 3114 5 79162381 84825422
3071 5 79162381 82676901 3115 5 79162381 84825763
3072 5 79162381 82883691 3116 5 79162381 84825942
3073 5 79162381 82954942 3117 5 79162381 84843411
3074 5 79162381 82971688 3118 5 79162381 84936441
3075 5 79162381 83023965 3119 5 79162381 84936493
3076 5 79162381 83094205 3120 5 79162381 84943705
3077 5 79162381 83146355 3121 5 79162381 169454950
3078 5 79162381 83280630 3122 5 79162381 181522829
3079 5 79162381 83281412 3123 5 79162301 204759879
3380 5 79162381 83400242 3124 5 79162381 209874191
3081 5 79162381 83405797 3125 5 79175814 79176557
3082 5 79162381 83437132 3126 5 79175814 79188028
3083 5 79162381 83522252 3127 5 79175814 79201760
3084 5 79162381 83560095 3128 5 79175814 79230005
3085 5 79162381 83560204 3129 5 79175814 79230318
3086 5 79162381 83572400 3130 5 79175814 79505592
3087 5 79162381 83607661 3131 5 79175814 79510072
3088 5 79162381 83745342 3132 5 79175814 79538012
3089 5 79162381 83861275 3133 5 79175814 79538048
3090 5 79162381 83861633 3134 5 79175814 79538367
145
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
'fable 1 (contd.)
Chromosomal Chromosomal
Segment Chr, 13oundaryl Boundary2 Segment Chr. Boundary1 Boundary2
3135 5 79175814 79669824 3179 5 79175814 81854583
3136 5 79175814 79682242 3180 5 79175814 81859374
3137 5 79175814 79699261 3181 5 79175814 81861368
3138 5 79175814 79710673 3182 5 79175814 81863686
3139 5 79175814 79861902 3183 5 79175814 81916850
3140 5 . 79175814 79867710 3184 5 79175814 81954891
3141 5 79175014 79867868 3185 5 79175814 81985250
3142 5 79175814 79867873 3186 5 79175814 82083752
3143 5 79175614 79961961 3187 5 79175814 82101253
3144 5 79175814 80086268 3188 5 79175814 82143124
3145 5 79175814 80190673 3189 5 79175814 82236318
3146 5 79175814 = 80190777 3190 5 79175814
82325587
3147 5 79175814 80192546 3191 5 79175814 82427210
3148 5 79175814 80195395 3192 5 /9175814 82431853
3149 5 79175814 80199923 3193 5 79175814 82446714
3150 5 79175814 80241911 3194 5 79175814 82446794
3151 5 79175814 80282785 3195 5 79175814 82551111
3152 5 79175814 80345337 3196 5 79175814 82552090
, 3153 5 79175814 80389787 3197 5 79175814
82555641
3154 5 79175814 80411639 .3198 5 79175814 82555670 '
3155 5 79175814 80446855 3199 5 79175814 82556511
3156 5 79175814 80492790 3200 5 79175814 82559047,
3157 5 79175814 80670554 3201 5 79175814 82561535
3158 5 79175814 80674679 3202 5 79175814 82610100
3159 5 79175814 80720509 3203 5 79175814 82676822
3160 5 79175814 80800856 3204 5 79175814 82676901
3161 5 79175814 80804587 3205 5 79175814 82883691
3162 5 79175814 80807409 3206 5 79175814 82954942
3163 5 79175814 80835734 3207 5 79175814 82971688
. 3164 5 79175814 80971764 3208 5 79175814
83023965
3165 5 79175814 80972258 3209 5 79175814 83094205
3166 5 79175814 80974450 3210 5 79175814 83146355
3167 5 79175814 81047638 3211 5 79175814 83280630
3168 5 79175814 81082921 3212 5 79175814 83281412
3169 5 79175814 81157909 3213 5 79175814 83400242
3170 5 79175814 81265937 3214 5 79175814 83405797
3171 5 79175814 81265937 3215 5 79175814 83437132
3172 5 79175814 81267485 3216 5 79175814 83522252
3173 5 79175814 81267499 . 3217 5 79175814 83560095
3174 5 79175814 81274512 3218 5 79175814 83560204
3175 5 79175814 81763618 3219 5 79175814 83572400
3176 5 79175814 81797217 3220 5 79175814 83607661
3177 5 79175814 81800186 3221 5 79175814 83745342
3178 5 79175814 81806213 3222 5 79175814 83861275
146
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chrmnoomng
Segment Chr. Boundary]. Boundary2 Segment Chr. Boundary1 Boundary2
3223 5 79175814 83861633 3267 5 79183135
79669824
3224 5 79175814 83865653 3268 5 79183135
79682242
3225 5 79175814 83865914 3269 5 79183135
79699261
3226 5 79175814 83865920 3270 5 79183135
79710673
3227 5 79175814 83868010 3271 5 79183135
79861902
3228 5 79175814 84019752 3272 5 79183135
79867710
3229 5 79175814 84065912 3273 5 79183135
79867868
3230 5 79175814 84086632 3274 5 79183135
79867873
3231 5 79175614 04089603 3275 9 79183135
79961961
3232 5 79175814 84104814 3276 5 79183135
80086268
3233 5 79175814 84105175 3277 5 79183135
80190671
3234 5 79175814 84251635 1278 5 79183135
80190777
3235 5 79175814 84252180 3279 5 79183135
80192546
3236 . 5 79175814 84253030 3280 5 79183135 80195395
3237 5 79175814 84254208 3281 5 79183135
80199923
3238 5 79175814 84314930 3282 5 79183135
80241911
3239 5 79175814 84340523 3283 5 79183135
80282785
3240 5 79175814 84516140 3284 5 79183135
80345337
3241 5 79175814 84706916 3285 5 79183135
80389787
3242 5 79175814 84799488 3286 5 79183135
80411639
3243 5 79175814 84801081 3287 5 79183135
80446855
3244 5 79175814 84824103 3288 5 79183135
80492790
3245 5 79175814 84824203 3289 5 79183135
80670554
3246 5 79175814 84824816 3290 5 79183135
80674679
3247 5 79175814 84825422 3291 5 79183135
80720509
3248 5 79175814 84825763 3292 5 79183135
80800856
3249 5 79175814 84825942 3293 5 79183135
80804587
3250 5 79175814 84843411 3294 5 79183135
80807409
3251 5 79175814 84936441 3295 5 79183135
80835734
3252 5 79175814 84936493 3296 5 79183135
80971764
3253 5 79175814 84943705 3297 5 79181115
80972258
3254 5 79175814 169454950 3298 5 79183135
80974450
3255 5 79175814 181522829 3299 5 79183135
81047638
3256 5 79175814 204759879 3300 5 79183135
81082921
3257 5 79175814 209874191 3301 5 79183135
81157909
3258 5 79183135 79188028 3302 5 79183135
81265937
3259 5 79183135 79201760 3303 5 79183135
81265937
3260 5 79183135 79230005 3304 5 79183135
81267485
3261 5 79183135 79230318 3305 5 79183135
81267499
3262 5 79183135 79505592 3306 5 79183135
81274512
3263 5 79183135 79510072 3307 5 79183135
81763618
3264 5 79183135 79538012 3308 5 79183135
81797217
3265 5 79183135 79538048 3309 5 79183135
81800186
3266 5 79183135 79538367 3310 5 79183135
81806213
147
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
ChromosmnM Chromosomal
Segment Cbt Boundmyl Boundary2 Segment Cir. Boundary1
Boundary 2
3311 5 79183135 81654583 3355 5 79183135
83861633
3312 5 79183135 81859374 3356 5 79183135
83865653
3313 5 79183135 81861348 3357 5 79183135
83865914
3314 5 79183135 81863686 3358 5 79183135
83865920
3315 5 79183135 81916850 3359 5 79183135
83868010
3316 5 79183135 81954891 3360 5 79183135
84019752
3317 5 79183135 81985250 3361 5 79183135
84065912
3318 5 79183135 82083752 3362 5 79183135
84086632
3319 5 79183135 82101253 3363 5 79183135
84089603
3320 5 79183135 82143124 3364 5 79183135
84104814
3321 5 79183135 82236318 3365 5 ' 79183135
84105179
3322 5 79183135 82325587 3366 5 79183135
84251635
3323 5 79181135 82427210 3367 5 79183135
84252180
3324 5 79183135 82431853 3368 5 79183135
84253030
3325 5 79183135 82446714 3369 .5 79183135
84254208
3326 5 79183135 82446794 3370 5 79183135
84314930
3327 5 79183135 82551111 3371 5 79183135
84340523
3328 5 79183135 82552090 3372 5 79183135
84516340
3329 5 79183135 82555641 3373 5 79183135
84706916
3330 5 79183135 82555670 3374 5 79183135
84799488
3331 5 79183135 82556511 3375 5 79183135
84801081
3332 5 79183135 82559047 3376 5 79183135
84824103
3333 5 79183135 82561535 3377 5 79183135
84824203
3334 5 79183135 82610100 3378 5 79183135
84824816
3335 5 79183135 82676822 3379 5 79183135
84825422
3336 5 79183135 82676901 3380 5 79183135
84825763
3337 5 79183135 82883691 3381 5 79183135
84825942
3338 5 79183135 82954942 3382 5 79183135
84843411
3339 5 79183135 82971688 3383 5 79183135
84936441
3340 5 79183135 83923965 3384 5 79183135
84936493
3341 5 79183135 83094205 3385 5 791111135
84943705
3342 5 79183135 83146355 3386 5 79183135
169454950
3343 5 79183135 83280630 3387 5 79183135
181522829
3344 5 79183135 83281412 3388 5 79183135
204759879
3345 5 79183135 83400242 3389 5 79183135
209874191
3346 5 79183135 83405797 3390 5 79200056
79201760
3347 5 79183135 83437132 3391 5 79200056
79230005
3348 5 79183135 83522252 3392 5 79200056
79230318
3349 5 79183135 83560095 3393 5 79200056
79505592
3350 5 79183135 83560204 3394 5 79200056
79510072
3351 5 79183135 83572400 3395 5 79200056
79538012
3352 5 79183135 83607661 3396 5 79200056
79538048
3353 5 79183135 83745342 3397 5 79200056
79538367
3354 5 79183135 83861275 3398 5 79200056
79669824
148
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (cont'cl.) .
Chmmommnal Chmmosmnal
Segment CM. Boundary] Boundary2 Segment Om Boundary 1
Beundary2
3399 5 79200056 79682242 3443 5 79200056
81859374
3400 5 79200056 79699261 3444 5 79200056
81861368
3401 5 79200056 79710673 3445 5 79200056
81863686
3402 5 79200056 79861902 3446 5 79200056
81916850
3403 5 79200056 79867710 3447 5 79200056
81954891
3404 5 79200056 79867868 3448 5 79200056
81985250
3405 5 79200056 79867873 3449 5 79200056
82083752
3406 5 79200056 79961961 3450 5 79200056
82101253
3407 5 79200056 80086268 3451 5 79200056
82143124
3408 5 79200056 80190673 3452 5 79200056
82236318
3409 5 79200056 80190777 . 3453 5 79200056
82325587
3410 5 79200056 80192546 3454 5 79200056
82427210
3411 5 79200056 80195395 3455 5 79200056
82431853
3412 5 79200056 80199923 3156 5 79200056
82446714
3413 5 79200056 80241911 3457 5 79200056
82446794
3414 5 79200056 80282785 3458 5 79200056
82551111
3415 5 79200056 80345337 3459 5 79200056
82552090
3416 5 79200056 80389787 3460 5 79200056
82555641
3417 5 79200056 80411639 3461 5 79200056
82555670
3418 5 79200056 80446855 3462 5 79200056
82556511
3419 5 79200056 80492790 3463 5 79200056
82559047
3420 5 79200056 80670554 3464 5 79200056
82561535
3421 5 79200056 80674679 3465 5 79200056
82610100
3422 5 79200056 80720509 3466 5 79200056
82676822
3423 5 79200056 80800856 3467 5 79200056
82676901
3424 5 79200056 80804587 3468 5 79200056
82883691
3425 5 79200056 80807409 3469 5 79200056
82954942
3426 5 79200056 80835734 3470 5 79200056
82971688
3427 5 79200056 80971764 3471 5 79200056
83023965
3428 5 79200056 80972258 3472 5 79200056
83094209
3429 5 79200056 80974450 3473 5 79200056
83146355
3430 5 79200056 81047638 3474 5 79200056
83200630
3431 5 79200056 81082921 3475 5 79200056
83281412
3432 5 79200056 81157909 3476 5 79200056
83400242
3433 5 79200056 81265937 3477 5 79200056
83405797
3434 9 79200056 81265937 3478 5 79200056
83437132
3435 5 79200056 81267485 3479 5 79200056
83522252
3436 5 79200056 81267499 3480 5 79200056
83560095
3437 5 79200056 81274512 3481 5 79200056
83560204
3438 5 79200056 81763618 3482 5 79200056
83572400
3439 5 79200056 81797217 3483 5 79200056
83607661
3440 5 79200056 81800186 3484 5 79200056
83745342
3441 5 79200056 81806213 3485 5 79200056
83861275
3442 5 79200056 81854583 3486 5 79200056
83861633
149
CB 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chmmosonud
Segment Cho. Boundaryl Boundary 2 Segment Chn Boundary 1
Boundary2
3487 5 79200056 83865653 3531 5 79229010
79710673
3488 5 79200056 83865914 3532 5 79229010
79861902
3489 5 79200056 83865920 3533 5 79229010
79867710
3490 5 79200056 83868010 3534 5 79229010
79867868
3491 5 79200056 84019752 3535 5 79229010
79867873
3492 5 79200056 84065912 3536 5 79229010
79961961
3493 5 79200056 84086632 3537 5 79229010
80086268
3494 5 79200056 84089603 3538 5 79229010
80190673
3495 5 I 79200056 84104814 3539 5 79229010
80190777
3496 5 79200056 84105175 3540 5 79229010
80192546
3497 5 79200056 84251635 3541 5 79229010
80195395
3498 5 79200056 84252180 3542 5 79229010
80199923
3499 5 79200056 84253030 3543 5 79229010
80241911
3500 5 79200056 84254208 3544 5 79229010
80282785
3501 5 79200056 84314930 3545 5 79229010
80345337
3502 5 79200056 84340523 3546 5 79229010
80389787
3503 5 79200056 84516340 3547 5 79229010
80411639
3504 5 79200056 84706916 3548 5 79229010
80446855
3505 5 79200056 84799488 3549 5 79229010
80492790
3506 5 79200056 84801081 3550 5 79229010
80670554
3507 5 79200056 84824103 3551 5 79229010
80674679
3508 5 79200056 84824203 3552 5 79229010
80720509
3509 5 79200056 84824816 3553 5 79229010
80800856
3510 5 79200056 14825422 3554 5 79229010
80804587
3511 5 79200056 84825763 3555 = 5 79229010
10807409
3512 5 79200056 84825942 3556 5 79229010
80835734
3513 5 79200056 84843411 3557 5 79229010
80971764
3514 5 79200056 84936441 3558 5 79229010
80972258
3515 5 79200056 84936493 3559 5 79229010
80974450
3516 5 79200056 84943705 3560 5 79229010
81047638
3517 5 79200056 169454950 3561 5 79229010
81082921
3518 5 79200056 181522829 3562 5 79229010
81157909
3519 5 79200056 204759879 3563 5 79229010
81265937
3520 5 79200056 209874191 3564 5 79229010
81265937
3521 5 79229010 79230005 3565 5 79229010
81267485
3522 5 79229010 79230318 3566 5 79229010
81267499
3523 5 79229010 79505592 3567 5 79229010
81274512
3524 5 79229010 79510072 3568 5 79229010
81763618
3525 5 79229010 79538012 3569 5 79229010
81797217
3526 5 79229010 79538048 3570 5 79229010
81800186
3527 5 79229010 79538367 3571 5 79229010
81806213
3528 5 79229010 79669824 3572 5 79229010
81854583
3529 5 79229010 79682242 3573 5 79229010
81859374
3530 5 79229010 79699261 3574 5 79229010
81861368
150
CA 02 9 3 95 8 0 2 0 16 -08 -11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
fluonnsonat Chromonnual
Sopneit Cho. Boundary! Boundary 2 Segment Ch, Boundary1
Boundani2
3575 5 79229010 81863686 3619 5 79229010
83865920
3576 5 79229010 81916850 3620 5 79229010
83868010
3577 5 79229010 81954891 3621 5 79229010
84019752
3578 5 79229010 81985250 3622 5 79229010
84065912
3579 5 79229010 82083752 3623 5 79229010
84086632
3580 5 79229010 82101253 3624 5 79229010
84089603
3581 5 79229010 82143124 3625 5 79229010
84104814
3582 5 79229010 82236318 3626 5 79229010
84105175
3583 5 79229010 82325587 3627 5 79229010
84251635
3584 5 79229010 82427210 3628 5 79229010
84252180
3585 5 79229010 82431853 3629 5 79229010
84253030
3586 5 79229010 82446714 3630 5 79229010
84254208
3587 5 79229010 82446794 3631 5 79229010
84314930
3588 5 79229010 82551111 3632 5 79229010
84340523
3589 5 79229010 62552090 3633 5 79229010
84516340
3590 5 79229010 62555641 3634 5 79229010
84706916
3591 5 79229010 82555670 3635 5 79229010
84799488
3592 5 79229010 62556511 3636 5 79229010
84801081
3593 5 79229010 82559047 3637 5 79229010
84824103
3594 5 79229010 82561535 3638 5 79229010
84824203
3595 5 79229010 82610100 3639 5 79229010
84824816
3596 5 79229010 82676822 3640 5 79229010
84825422
3597 5 79229010 82676901 3641 5 79229010
84825763
3598 5 79229010 82883691 3642 5 79229010
84825942
3599 5 79229010 82954942 3643 5 79229010
84843411
3600 5 79229010 82971688 3644 5 79229010
84936441
3601 5 79229010 83023965 3645 5 79229010
84936493
3602 5 79229010 83094205 3646 5 79229010
84943705
3603 5 79229010 83146355 3647 5 79229010
169454950
3604 5 79229010 83280630 3648 5 79229010
181522829
3605 5 79229010 83281412 3649 5 79229010
204759879
3606 5 79229010 83400242 3650 5 79229010 209874191
3607 5 79229010 83405797 3651 5 79229019
79230005
3608 5 79229010 83437132 3652 5 79229019
79230318
3609 5 79229010 83522252 3653 5 79229019
79505592
3610 5 79229010 83560095 3654 5 79229019
79510072
3611 5 79229010 83560204 3655 5 79229019
79538012
3612 5 79229010 83572400 3656 5 79229019
79538048
3613 5 79229010 83607661 3657 5 79229019
79538367
3614 5 79229010 83745342 3658 5 79229019
79669824
3615 5 79229010 83861275 3659 5 79229019
79682242
3616 5 79229010 83861633 3660 5 79229019
79699261
3617 5 79229010 83865653 3661 5 79229019
79710673
3618 5 79229010 83865914 3662 5 79229019
79861902
151
CA 02 9 3 958 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table I (Goad.)
Chromosomal Chromosomal
Segment Cho. Boundary 1 Boundary 2 Segment Chr
Boundary 1 Boundary 2
3663 5 79229019 79867710 3707 5 79229019
81954891
3664 5 79229019 79867868 3708 5 79229019
81985250
3665 5 79229019 79867873 3709 5 79229019
82083752
3666 5 79229019 79961961 3710 5 79229019
82101253
3667 5 79229019 80086268 3711 5 79229019
82143124
3668 5 79229019 80190673 3712 5 79229019
82236318
3669 5 79229019 80190777 3713 5 79229019
82325587
3670 5 79229019 80192546 3714 5 79229019
82427210
3671 5 79229019 80195395 - 3715 5 79229019
82431853
3672 5 79229019 80199923 3716 5 79229019
82446714
3673 5 79229019 80241911 3717 5 79229019
82446794
3674 5 79229019 80282785 3718 5 79229019
82551111
3675 5 79229019 80345337 3719 5 79229019
82552090
3676 5 79229019 80389787 1720 5 79229019
82555641
3677 5 79229019 80411639 3721 5 79229019
82555670
3678 5 79229019 80446855 3722 5 79229019
82556511
3679 5 79229019 60492790 3723 5 79229019
82559047
3680 5 79229019 80670554 3724 5 79229019
82561535
3681 5 79229019 80674679 3725 5 79229019
82610100
3682 5 79229019 80720509 3726 5 79229019
82676822
3683 5 79229019 80800856 3727 5 79229019
82676901
3684 5 79229019 80804587 3728 5 79229019
82883691
3685 5 79229019 80807409 3729 5 79229019
82954942
3686 5 79229019 80835734 3730 5 79229019
82971688
3687 5 79229019 80971764 3731 5 79229019
83023965
3688 5 79229019 80972258 3732 5 79229019
83094205
3689 5 79229019 80974450 3733 5 79229019
83146355
3690 5 79229019 81047638 1734 5 79229019
83280630
3691 5 79229019 81082921 3735 5 79229019
83281412
3692 5 79229019 81157909 3736 5 79229019
83400242
3693 5 79229019 81265937 3737 5 79229019
83405797
3694 5 79229019 81265937 3738 5 79229019
83437132
3695 5 79229019 81267485 3739 5 79229019
8.1522252
3696 5 79229019 81267499 3740 5 79229019
83560095
3697 5 79229019 81274512 3741 5 79229019
83560204
3698 5 79229019 81763618 3742 5 79229019
83572400
3699 5 79229019 81797217 3743 5 79229019
83607661
3700 5 79229019 81800186 3744 5 79229019
83745342
3701 5 79229019 81806213 3745 5 79229019
83861275
3702 5 79229019 811854583 3746 5 79229019
83861633
3703 5 79229019 81859374 3747 5 79229019
83865653
3704 5 79229019 81861368 3748 5 . 79229019
83865914
3705 5 79229019 81863686 3749 5 79229019
83865923
3706 5 79229019 81916850 3750 5 79229019
83868010
152
CA 02 9 3 95 8 0 2 016 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
,
Chromosomal Chromosomal
Segment Chr, Bounday1 Boundary2 Segment am Boundary] Boundary2
3751 5 79229019 84019752 3795 5 79503885 80086268
3752 5 79229019 84065912 3796 5 79503885 80190673
3753 5 79229019 84086632 3797 5 79503885 80190777
'
3754 5 79229019 84089601 3798 5 79503885 80192546
3755 5 79229019 84104814 3799 5 79503885 80195395
3756 5 79229019 84105175 3800 5 79503885 80199923
3757 5 79229019 84251635 3801 5 79503885 80241911
3758 5 79229019 84252180 3802 5 79503885 80282785
3759 5 79229019 84253030 3801 5 79503885 80345337
' 3760 5 79229019 84254208 3804 5 79503885 80389787
3761 5 79229019 84314930 3805 5 79503885 80411639
3762 5 79229019 84340523 3806 5 79503885 80446855
3763 5 79229019 84516340 3807 5 79503885 80492790
3764 5 79229019 84706916 3808 5 79503885 80670554
3765 5 79229019 84799488 3809 5 79503885 80674679
3766 5 79229019 84801081 _3810 5 79503885 80720509
3767 5 79229019 84824103 3811 5 79503885 80600856
3768 5 79229019 84824203 3812 5 79503885 80804587
3769 5 79229019 84824816 3813 5 79503885 80807409
3770 5 79229019 84825422 3814 5 79503885 80835734
3771 5 79229019 84825763 3815 5 79503885 80971764
3772 5 79229019 84825942 3816 5 79501685 80972250
3773 5 79229019 84843411 3817 5 79503885 80974450
3774 5 79229019 84936411 3818 5 79503885 81047638
3775 5 79229019 84936493 3819 5 79503885 81082921
3776 5 79229019 84943705 3820 5 79503885 81157909
3777 5 79229019 169454950 3821 5 79503885 81265937
3778 5 79229019 181522829 3822 5 79501885 81265937
3779 5 79229019 204759879 3823 5 79503885 81267485
3780 5 79229019 209874191 3824 5 79503885 81267499
3781 5 79503885 79505592 3825 5 79503885 81274512
3782 5 79503885 79510072 3826 5 79503885 81763618
3783 5 79503885 79538012 3827 5 79503885 81797217
3784 5 79503885 79538048 3828 5 79503885 81800186
3785 5 79503885 79538367 3829 5 79503885 81806213
3786 5 79503885 79669824 3830 5 79503885 81854583
3787 5 79503885 79682242 3831 5 79503885 81859374
3788 5 79503885 79699261 3832 5 79503885 81861368
3789 5 79503885 79710673 3833 5 79503885 81863686
3790 5 79503085 79861902 3834 5 79503885 81916850
3791 5 79503885 79867710 3835 5 79503885 81954891
3792 5 79503885 79867868 3936 5 79503885 81985250
3793 5 79503885 79867873 3837 5 79503885 82083752
3794 5 79503885 79961961 3838 5 79503885 82101253
153
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (confd.)
Chromosomal Chromosomal
Segment Chr Boundmy1 Boundary2 Segment Chr. Boundmyl Boundary2
3839 5 79503885 82143124 1883 5 79503885 84104814
3840 5 79503885 82236318 3884 5 79503885 84105175
3841 5 79503885 82325587 3885 5 79503885 84251635
3842 5 79503885 02427210 3886 5 79503885 84252180
3843 5 79503885 82431853 3887 5 79503885 84253030
3844 5 79503885 82446714 3888 5 79503885 84254208
3845 5 79503885 82446794 3889 5 79503885 84314930
3846 5 79503885 82551111 3890 5 79503885 84340523
3847 5 79503885 82552090 3891 5 79503885 84516340
3848 5 79503885 82555641 3892 5 79503885 84706916
3849 5 79503885 82555670 3893 5 79503885 84799488
3850 5 79503885 82556511 3894 5 79503885 84801081
3851 5 79503805 82559047 3895 5 79503885 84824103
3852 5 79503885 82561535 3896 5 79503885 84824203
3853 5 79503885 82610100 3897 5 79503885 84824816
3854 5 79503885 82676822 3898 5 79503885 84825422
3855 5 79503885 82676901 3899 5 79503885 84825763
3856 5 79503885 82883691 3900 5 79503885 84825942
3857 5 79503885 82954942 3901 5 79503885 84843411
3858 5 79503885 82971688 3902 5 79503885 84936441
3859 5 79503885 83023965 3903 5 79503885 84936493
3860 5 79503885 83094205 3904 5 79503885 84943705
3861 5 79503885 83146355 3905 5 79503885 169454950
3862 5 79503885 83280630 3906 5 79503885 181522829
3863 5 79503885 83281412 3907 5 79503885 204759879
3864 5 79503885 83400242 3908 5 79503885 209874191
3865 5 79503885 83405797 3909 5 79505757 79505592
3866 5 79503885 83437132 3910 5 79505757 79510072
3867 5 79503885 83522252 3911 5 79505757 79538012
3868 5 79503885 83560095 3912 5 79505757 79538048
3869 5 79503885 83560204 3913 5 79505757 79538367
' 3870 5 79503885 83572400 3914 5 79505757
79669824
3871 5 79503885 83607661 3915 5 79505757 79682242
3872 5 79503885 83745342 3916 5 79505757 79699261
3873 5 79503885 83861275 3917 5 79505757 79710673
3874 5 79503885 83861633 3918 5 79505757 79861902
3875 5 79503885 83865653 3919 5 79505757 79867710
,
3676 5 79503885 83865914 3920 5 79505757 79867868
3877 5 79503885 83865920 3921 5 79505757 79867873
3878 5 79503885 83868010 3922 5 79505757 79961961
3879 5 79503885 84019752 3923 5 79505757 80086268
3880 5 79503885 84065912 3924 5 79505757 80190673
3881 5 79503885 84086632 3925 5 79505757 80190777
3882 5 79503885 84089603 3926 5 79505757 80192546
154
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Clumnosonml Chromosomal
Segment CM. Boundary 1 Boumdmy2 Segment CM. Boundary1
Boundary2
3927 5 79505757 80195395 3971 5 79505757
82431853
3928 5 79505757 80199923 3972 5 79505757
82446714
3929 5 79505757 80241911 3973 5 79505757
82446794
3930 5 79505757 80282785 3974 5 79505757
82551111
3931 5 79505757 80345337 3975 5 79505757
82552090
3932 5 79505757 80389787 . 3976 5 79505757
82555641
3933 5 79505757 80411639 3977 5 79505757
82555670
3934 5 79505757 80446855 3978 5 79505757
82556511
3935 5 79505757 80492790 3979 5 79505757
82559047
3936 5 79505757 80670554 3980 5 79505757
82561535
3937 5 79505757 80674679 3981 5 79505757
82610100
3938 5 79505757 80720509 3982 5 79505757
82676822
3939 5 79505757 80800856 3983 5 79505757
82676901
3940 5 79505757 80804587 3984 5 79505757
82883691
3941 5 79505757 80807409 3985 5 79505757
82954942
3942 5 79305757 80835734 3986 5 79505757
82971688
3943 5 79505757 80971764 3987 5 79505757
83023965
3944 5 79505757 80972258 3988 5 79505757
83094205
3945 5 79505757 80974450 3989 5 79505757
83146355
3946 5 79505757 61047638 3990 5 79505757
83280630
3947 5 79505757 81082921 3991 5 79505757
83281412
3948 5 79505757 81157909 3992 5 79505757
83400242
3949 5 79505757 81265937 3993 5 79505757
83405797
3950 5 79505757 81265937 3994 5 79505757
83437132
3951 5 79505757 81267485 3995 5 79505757
83522252
3952 5 79505757 81267499 3996 5 79505757
83560095
3953 5 79505757 81274512 3997 5 79505757
83560204
3954 5 79505757 81763618 3998 5 79505757
83572400
3955 5 79505757 81797217 3999 5 79505757
83607661
3956 5 79505757 81800186 4000 5 79505757
83745342
3957 5 79505757 81806213 4001 5 79505757
83861275
3958 5 79505757 81854583 4002 5 79505757
83861633
3959 5 79505757 81859374 4003 5 79505757
83865653
3960 5 79505757 81861368 4004 5 79505757
83865914
3961 5 79505757 81863686 4005 5 79505757
83865920
3962 5 79505757 81916850 4006 5 79505757
83868010
3963 5 79505757 81954891 4007 5 79505757
84019752
3964 5 79505757 81985250 4008 5 79505757
84065912
3965 5 79505757 82083752 4009 5 79505757
84086632
3966 5 79505757 82101253 4010 5 79505757
84089603
3967 5 79505757 82143124 4011 5 79505757
84104814
3968 5 79505757 82236318 4012 5 79505757
84105175
3969 5 79505757 82325587 4013 5 79505757
84251635
3970 5 79505757 82427210 4014 5 79505757
84252180
155 .
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chrmnosmnal
Segment Cho. Boundary! Boundary 2 Segment Chr.
Boundary! Boundary2
4015 5 79505757 84253030 4059 5 79531009 80411639
4016 5 79505757 84254208 4060 5 79531009 80446855
4017 5 79505757 84314930 4061 5 79531009 80492790
4018 5 79505757 84340523 4062 5 79531009 80670554
4019 5 79505757 84516340 4063 5 79531009 80674679
4020 5 79505757 84706916 4064 5 79531009 80720509
4021 5 79505757 84799488 4065 5 79531009 80800856
4022 5 79505757 84801081 4066 5 79531009 80804587
4023 5 79505757 84824103 4067 5 79531009 80807409
4024 5 79505757 84824203 4068 5 79531009 80835734
4025 5 79505757 84824816 4069 5 79531009 80971764
4026 5 79505757 84825422 4070 5 79531009 80972258
4027 5 79505757 84825763 4071 5 79531009 80974450
4028 5 79505757 84825942 4072 5 79531009 81047618
4029 5 79505757 84843411 4073 5 79531009 81082921
4030 5 79505757 84936411 4074 5 79531009 81157909
4031 5 79505757 84936493 4075 5 79531009 81265937
4032 5 79505757 84943705 4076 5 79531009 81265937
4033 5 79505757 169454950 4077 5 79531009 81267485
4034 5 79505757 181522829 4078 5 79531009 81267499
4035 5 79505757 254759879 4079 5 79531009 81274512
4036 5 79505757 209874191 4080 5 79531009 81763618
4037 5 79531009 79538012 4081 5 79531009 81797217
4038 5 79531009 79538048 4082 5 79531009 81800186
4039 5 79531009 79538367 4083 5 79531009 81806213
4040 5 79531009 79669824 4084 5 79531009 81854583
4041 5 79531009 79682242 4085 5 79531009 81859374
4042 5 79531009 79699261 4086 5 79531009 81861368
4043 5 79531009 79710673 4087 5 79531009 81863686
4044 5 79531009 79861902 4088 5 79531009 81916850
4045 5 79531009 79867710 4089 5 79531009 81954891
4046 5 79531009 79867868 4090 5 79531009 81985250
4047 5 79531009 79867873 4091 5 79531009 82083752
4048 5 79531009 79961961 4092 5 79531009 82101253
4049 5 79531009 80086268 4093 5 79531009 82143124
4050 5 79531009 80190673 4094 5 79531009 82236318
4051 5 79531009 80190777 4095 5 79531009 82325587
4052 5 79531009 80192546 4096 5 79531009 82427210
4053 5 79531009 80195395 4097 5 79531009 82431853
4054 5 79531009 80199923 4098 5 79531009 82446714
4055 5 79531009 80241911 4099 5 79531009 82446794
4056 5 79531009 80282785 4100 5 79531009 82551111
4057 5 79531009 80345337 4101 5 79531009 82552090
4058 5 79531009 80389787 4102 5 79531009 82555641
156
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
chromosomal Chromosomal
Segrnent CIL Boundaryl Bkmadaof2 Segment Chu Boundaryl Boundary2
4103 5 79531009 82555670 4147 5 79531009 84799488
4104 5 79531009 82556511 4148 5 79531009 84801081
4105 5 79531009 82559047 4149 5 79531009 84824103
4106 5 79531009 82561535 4150 .. 5 .. 79531009 .. 84824203
4107 5 79531009 82610100 4151 .. 5 .. 79531009 .. 84824816
4108 5 79531009 82676822 4152 5 79531009 84825422
=
4109 5 79531009 82676901 4153 5 79531009 84825763
4110 5 79531009 82883691 4154 5 79531009 84825942
4111 5 79531009 82954942 4155 5 79531009 84843411
4112 5 79531009 82971688 4156 5 79531009 84936441
4113 5 79531009 83023965 4157 5 79531009 84936493
4114 5 79531009 83094205 4158 5 79531009 84943705
4115 5 79531009 83146355 4159 5 79531009 169454950
4116 5 79531009 83280630 4160 5 79531009 181522829
4117 5 79531009 83281412 4161 5 79531009 204759879
4118 5 79531009 83400242 4162 5 79531009 209874191
4119 5 79531009 83405797 4161 5 7.9531040 79538012
4120 5 79531009 83437132 4164 5 79531040 79538048
4121 5 79531009 83522252 4165 5 79531040 79538367
4122 5 79531009 83560095 4166 5 79531040 79669824
4123 5 79531009 83560204 4167 .. 5 .. 79531040 .. 79682242
4124 5 79531009 83572400 4168 5 79531040 79699261
4125 5 79531009 83607661 4169 5 79531040 79710673
4126 5 79531009 83745342 4170 5 79531040 79861902
4127 5 79531009 83861275 4171 5 79531040 79867710
4128 5 79531009 83861633 4172 5 79531040 79867868
4129 5 79531009 83865653 4173 5 79531040 79867873
4130 5 79531009 83865914 4174 5 79531040 79961961
4131 5 79531009 83865920 4175 5 79531040 80086268
4132 5 79531009 83868010 4176 5 79531040 60190673
4133 5 79531009 84019752 4177 5 79531040 80190777
4134 5 79531009 84065912 4178 5 79531040 80192546
4135 5 79531009 84086632 4179 5 79531040 80195395
4136 5 79531009 84089603 4180 5 79531040 80199923
4137 5 79531009 84104814 4181 5 79531040 80241911
4138 5 79531009 84105175 4182 5 79531040 80282785
4139 5 79531009 84251635 4183 5 79531040 80345337
4140 5 79531009 84252180 4184 5 79531040 80389787
4141 5 79531009 84253030 4185 5 79531040 80411639
4142 5 79531009 84254208 4186 5 79531040 80446855
4143 5 79531009 84314930 4187 5 79531040 80492790
4144 5 79531009 84340523 4188 5 79531040 80670554
4145 5 79531009 84516340 4189 5 79531040 80674679
4146 5 79411009 84706916 4190 5 79531040 80720509
157
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'cL)
Canamosmnal Chromosomal
Segment Chr. Boundmyl Boundary2 Segment CM. Boundary 1
Bounclaly2
4191 5 79531040 80800856 4235 5 79531040
82676901
4192 5 79531040 80804587 4236 5 79531040
82883691
4193 5 79531040 80807409 4237 5 79531040
8.2954942
4194 5 79531040 80835734 4238 5 79531040
82971688
4195 5 79531040 80971764 4239 5 79531040
83023965
4196 5 79531040 80972258 4240 5 79531040
83094205
4197 = 5 79531040 80974450 4241 5 79531040
83146355
4198 5 79531040 81047638 4242 5 79531040
83280630
4199 5 79531040 81082921 4243 5 79531040
83281412
4200 5 79531040 81157909 4244 5 79531040
83400242
4201 5 79531040 81265937 4245 5 79531040
83405797
4202 5 79531040 81265937 4246 5 79531040
83437132
4203 5 79531040 61267485 4247 5 79531040
83522252
4204 5 79531040 81267499 4248 5 79531040
83560095
4235 5 79531040 81274512 4249 5 79531040
83560204
4206 5 79531040 81763618 4250 5 79531040
83572400
4207 5 79531040 81797217 4251 5 79531040
83607661
4208 5 79531040 81800186 4252 5 79531040
83745342
4209 5 79531040 81806213 4253 5 79531040
83861275
4210 5 79531040 81854583 4254 5 79531040
83061633
4211 5 79531040 81859374 4255 5 79531040
83865653
4212 5 79531040 81861368 4256 5 79531040
83865914
4213 5 79531040 81863686 4257 5 79531040
83865920
4214 5 79531040 81916850 4258 5 79531040
83868010
4215 5 79531040 81954891 4259 5 79531040
84019752
4216 5 79531040 81985250 4260 5 79531040
84065912
4217 5 79531040 82083752 4261 5 79531040
84086632
4218 5 79531040 82101253 4262 5 79531040
84089603
4219 5 79531040 82143124 4269 5 79531040
84104814
4220 5 79531040 82236318 4264 5 79531040
84105175
= 4221 5 79531040 82325587 4265 5
79531040 84251635
4222 5 79531040 82427210 4266 5 79531040
84252180
4223 5 79531040 82431853 4267 5 79531040
84253030
4224 5 79531040 82446714 4268 5 79531040
84254208
4225 5 79531040 82446794 4269 5 79531040
84314930
4226 5 79531040 82551111 4270 5 79531040
84340523
4227 5 79531040 82552090 4271 5 79531040
84516340
4228 5 79531040 82555641 4272 5 79531040
84706916
4229 5 79531040 82555670 4273 5 79531040
84799488
4230 5 79531040 82556511 4274 5 79531040
84801081
4231 5 79531040 82559047 4275 5 79531040
84824103
4232 5 79531040 82561535 4276 5 79531040
84824203
4233 5 79531040 82610100 4277 5 79531040
84824816
4234 5 79531040 82676822 4278 5 79531040
84825422
158
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/1JS2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Gm Boundary1 Boundary2 Segment Cho. Boundary 1
Boundary2
4279 5 79531040 84825763 4323 5 79537564 80974450
4280 5 79531040 84825942 4324 5 79537564 81047638
4281 5 79531040 84843411 4325 5 79537564 81082921
4282 5 79531040 84936441 4326 5 79537564 81157909
4283 5 79531040 84936493 4327 5 79537564 81265937
4284 5 79531040 84943705 4328 5 79537564 81265937
4285 5 79531040 169454950 4329 5 79537564 81267485
4286 5 79531040 181522829 4330 5 79537564 81267499
4287 5 79531040 204759879 4331 5 79537564 81274512
4288 5 79531040 209874191 , 4332 5 79537564 81763618
4289 5 79537564 79538012 4333 5 79537564 81797217
4290 5 79537564 79538048 4334 5 79537564 81800186
4291 5 79537564 79538367 4335 5 79537564 81806213
4292 5 79537564 79669824 4336 5 79537564 81854583
4293 5 79537564 79682242 4337 5 79537564 81859374
4294 5 79537564 79699261 4338 5 79537564 81861368
4295 5 79537564 79710673 4339 5 79537564 81863686
4296 5 = 79537564 79861902 4340 5 79537564 81916850
4297 5 79537564 79867710 4341 5 79537564 81954891
4298 5 79537564 79867868 4342 5 79537564 81985250
,
4299 5 79537564 79867873 4343 5 79537564 82083752
4300 5 79537564 79461961 4344 5 79537564 82101253
4301 5 79537564 80086268 4345 5 79537564 82143124
4302 5 79537564 80190673 4346 5 79537564 82236318
4303 5 79537564 80190777 4347 5 79537564 82325587
4304 . 5 79537564 80192546 4348 5 79537564 82427210
4305 5 79537564 80195395 4349 5 79537564 82431853
4306 5 79537564 80199923 4350 5 79537564 82446714
4307 5 79537564 80241911 4351 5 79537564 82446794
4308 5 79537564 80282785 4352 5 79537564 82551111
4309 5 79537564 80345337 = 4353 5 79537564 82552090
4310 5 79537564 80389787 4354 5 79537564 82555641
4311 5 79537564 80411639 4355 5 79537564 82555670
4312 5 79537564 80446855 4356 5 79537564 82556511
4313 5 79537564 80492790 4357 5 79537564 82559047
4314 5 79537564 80670554 4358 5 79537564 82561535
4315 5 79537564 80674679 4359 5 79537564 82610100
4316 5 79537564 80720509 4360 5 79537564 82676822
4317 5 79537564 80800856 4361 5 79537564 82676901
4318 5 79537564 80804587 4362 5 79537564 82883691
4319 5 79537564 80807409 4363 5 79537564 82954942
4320 5 79537564 80835734 4364 5 79537564 82971688
4321 5 79537564 80971764 4365 5 79537564 83023965
4322 5 79537564 80972258 4366 5 79537564 83094205
159
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (Coiled.)
Chromosomal Chromosomal
Segment an. Boundary 1 Boundaty2 Segment Chr. Boundary 1
Boundary2
4367 5 79537564 83146355 4411 5 79537564
169454950
4368 5 79537564 83280630 4412 5 79537564
181522829
4369 5 79537564 83281412 4413 5 79537564
204759679
4370 5 79537564 83400242 4414 5 79537564
209874191
4371 5 79537564 83405797 4415 5 79538367
79669824
4372 5 79537564 83437132 4416 5 79538367
79682242
4373 5 79537564 83522252 4417 5 79538367
79699261
4374 5 79537564 83560095 4418 5 79538367
79710673
4375 5 79537564 83560204 4419 5 79538367
79861902
4376 5 79537564 83572400 4420 5 79538367
79867710
4377 5 79537564 83607661 4421 5 79538367
79867868
4378 5 79537564 83745342 4422 5 79538367
79867873
4379 5 79537564 83861275 4423 5 79538367
79961961
4380 5 79537564 83861633 4424 5 79538367
80086268
4381 5 79537564 83865653 4425 5 79538367
80190673
4382 5 79537564 83865914 4426 5 79538367
80190777
4383 5 79537564 83865920 4427 5 79538367
80192546
4384 5 79537564 83868010 4428 5 79538367
80195395
4385 5 79537564 84019752 4429 5 79538367
80199923
4386 5 79537564 84065912 4430 5 79538367
80241911
4387 5 79537564 84086632 4431 5 79538367
80282785
4388 5 79537564 84009603 4432 5 79538367
80345337
4389 5 79537564 84104814 4433 5 79538367
80389787
4390 5 79537564 64105175 4414 5 79538367
80411639
4391 5 79537564 84251635 4435 5 79538367
80446855
4392 5 79537564 84252180 4436 5 79538367
80492790
4393 5 79537564 84253030 4437 5 79538367
80670554
4394 5 79537564 84254208 4438 5 79538367
80674679
4395 5 79537564 84314930 4439 5 79538367
80720509
4396 5 79537564 84340523 4440 5 79538367
80800856
4397 5 79537564 84516340 4441 5 79538367
10804587
4398 5 79537564 84706916 4442 5 79538367
80807409
4399 5 79537564 84799488 4443 5 79538367
80835734
4400 5 79537564 81601081 4444 5 79538367
80971764
4401 5 79537564 84824103 4445 5 79538367
80972258
4402 5 79537564 84824203 4446 5 79538367
80974450
4103 5 79537564 84824816 4447 5 79538367
81047638
4404 5 79537564 84825422 4448 5 79538367
81082921
4405 5 79537564 84825763 4449 5 79538367
81157909
4406 5 79537564 84825942 4450 5 79538367
81265937
4407 5 79537564 84843411 4451 5 79538367
81265937
4408. 5 79537564 84936441 4452 5 79538367 '
81267485
4409 5 79537564 84936493 4453 5 79538367
81267499
4410 5 79537564 84943705 4454 5 79538367
81274512
160
CA 02 9 3 958 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chtoutoseanal
Segment Cho. Boundary1 Boundary2 Segment Cho. Boundaryl Boundary2
4455 5 79538367 81763618 4499 5 79538367
83572400
4456 5 79538367 81797217 4500 5 79538367
83607661
4457 5 79538367 81800186 4501 5 79538367
83745342
4458 5 79538367 81806213 4502 5 79538367
83861275
4459 5 79538367 81854583 4503 5 79538367
81861633
4460 5 79538367 81859374 4504 5 79538367
83865653
4461 5 79538367 81861368 4505 5 79538367
83865914
4462 5 79538367 81863686 4506 5 79538367
83865920
4463 5 79538367 81916850 4507 5 79538367
83868010
4464 5 79538367 81954891 4508 5 79538367
84019752
4465 5 79538367 81985250 4509 5 79538367
84065912
4466 5 79538367 82083752 4510 5 79538367
84086632
4467 5 79538367 82101253 4511 5 79538367
84089603
4468 5 79538367 82143124 4512 5 79538367
84104814
4469 5 79538367 82236318 4513 5 79538367
84105175
4470 5 79538367 82325587 4514 5 79538367
84251635
4471 5 79538367 82427210 4515 5 79538367
84252180
4472 5 79538367 02431853 4516 5 79538367
84253030
4473 5 79538367 82446714 4517 5 79538367
84254208
4474 5 79538367 82446794 4518 5 79538367
84314930
4475 5 79538367 82551111 4519 5 79538367
84340523
4476 5 79538367 82552090 4520 5 79538367
84516340
4477 5 79538367 82555641 4521 5 79538367
84706916
4478 5 79538367 82555670 4522 5 79538367
84799488
4479 5 79538367 82556511 4523 5 79538367
84801081
4480 5 79538367 82559047 4524 5 79538367
84824103
4481 5 79538367 82561535 4525 5 79538367
84824203
4482 5 79538367 82610100 4526 5 79538367
84824816
4483 5 79538367 82676822 4527 5 79538367
84825422
4484 5 79538367 82676901 4528 5 79538367
84825763
4485 5 79538367 82883691 4529 5 79538367
84825942
4486 5 79538367 82954942 4530 5 79538367
84843411
4487 5 79538367 82971688 4531 5 79538367
84936441
4488 5 79538367 83023965 4532 5 79538367
84936493
4489 5 79538367 83094205 4533 5 79538367
84943705
4490 5 79538367 83146355 4534 5 79538367
169454950
4491 5 79538367 83280630 4535 5 79538367
181522829
4492 5 79538367 83281412 4536 5 79538367
204759879
4493 5 79538367 83400242 4537 5 79538367
209874191
4494 5 79538367 83405797 4538 5 79666742
79538367
4495 5 79538367 83437132 4539 5 79666742
79669824
4496 5 79538367 83522252 4540 5 79666742
79682242
4497 5 79538367 83560095 4541 5 79666742 '
79699261
4498 5 79538367 83560204 4542 5 79666742
79710673
161
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (confd.)
Chromosomal Chromosomal
Segment CM. Boundary 1 Boundary 2 Segment Chr. Boundary 1
Boundary 2
4543 5 79666742 79861902 4587 5 79666742
81916850
4544 5 79666742 79167710 4588 5 79666742
81954891
4545 5 79666742 79867868 4589 5 79666742
81985250
4546 5 79666742 79867873 4590 5 79666742
82083752
4547 5 79666742 79961961 4591 5 79666742
82101253
4548 5 79666742 80086268 4592 5 79666742
82143124
4549 5 79666742 80190673 4593 5 79666742
82236318
4550 5 79666742 80190777 4594 5 79666742
82325587
4551 5 79666742 80192546 4595 5 79666742
82427210
4552 5 79666742 80195395 4596 5 79666742
82431853
4553 5 79666742 80199923 4597 5 79666742
82446714
4554 5 79666742 80241911 4598 5 79666742
82446794
4555 5 79666742 80282785 4599 5 79666742
82551111
4556 5 79666742 80345337 4600 5 79666742
82552090
4557 5 79666742 80389787 4601 5 79666742
82555641
4558 5 79666742 80411639 4602 5 79666742
82555670
4559 5 79666742 80446855 4603 5 79666742
82556511
4560 5 79666742 80492790 4604 5 79666742
82559947
4561 5 79666742 80670554 4605 5 79666742
82561535
4562 5 79666742 80674679 4606 5 79666742
82610100
4563 5 79666742 80720509 4607 5 79666742
82676822
4564 5 79666742 80800856 4608 5 79666742
82676901
4565 5 79666742 80804587 4609 5 79666742
82883691
4566 5 79666742 80807409 4610 5 79666742
82954942
4567 5 79666742 80835734 4611 5 79666742
82971600
4568 5 79666742 80971764 4612 5 79666742
83023965
4569 5 79666742 80972258 4613 5 79666742
83094205
4570 5 79666742 80974450 4614 5 79666742
85146355
4571 5 79666742 81047638 4615 5 79666742
83714630
4572 5 79666742 81082921 4616 5 79666742
83281412
4573 5 79666742 81157909 4617 5 79666742
83400242
4574 5 79666742 81265937 4618 5 79666742
83405797
4575 5 79666742 81265937 4619 5 79666742
83437132
4576 5 79666742 81267485 4620 5 79666742
83522252
4577 5 79666742 81267499 4621 5 79666742
83560095
4578 5 79666742 81274512 4622 5 79666742
83560204
4579 5 79666742 81763618 4623 5 79666742
83572400
4580 5 79666742 81797217 4624 5 79666742
83607661
4581 5 79666742 81800186 4625 5 79666742
83745342
4582 5 79666742 81896213 4626 5 79666742
83861275
4583 5 79666742 81854583 4627 5 79666742
83861633
4584 5 79666742 81859374 4628 5 79666742
83865653
4585 5 79666742 81861368 4629 5 79666742
83865914
4586 5 79666742 81863686 4630 5 79666742
83865920
162
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Clr. Boundaryl Boundary2 Segment Chr. Bouadary1 Boundary2
4631 5 79666742 83868010 4675 5 79679654
80199923
4632 5 79666742 84019752 4676 5 79679654
80241911
4633 5 79666742 81065912 4677 5 79679654
80282785
4634 5 79666742 84086632 4678 5 79679654
80345337
4635 5 79666742 84089603 4679 5 79679654
80389787
4636 5 79666742 84104814 4680 5 79679654
80411639
,
4637 5 79666742 84105175 4681 5 79679654
80446855
4638 5 79666742 84251635 4682 5 79679654
80492790
4639 5 79666742 84252180 4683 5 79679654
80670554
4640 5 79666742 84253030 4684 5 79679654
80674679
4641 5 79666742 84254208 4685 5 79679654
80720509
4642 5 79666742 84314930 4686 5 79479654
80800856
4643 5 79666742 84340523 4687 5 79679654
80804587
4444 5 79666742 84516340 4688 5 79679654
80807409
4645 5 79666742 84706916 4689 5 79679654
80835734
4646 5 79666742 84799488 4690 5 79679654
80971764
4647 5 79666742 84801081 4691 5 79679654
80972258
4648 5 79666742 84824103 4692 5 79679654
80974450
4649 5 79666742 84824203 4693 5 79679654
81047638
4650 5 79666742 84824816 4694 5 79679654
81082921
4651 5 79666742 84825422 4695 5 79679654
81157909
4652 5 79666742 84825763 4696 5 79679654
81265937
4653 5 79666742 84825942 4697 5 79679654
81265937
4654 5 79666742 84841411 4698 5 79679654
81267485
4655. 5 79666742 84936441 4699 5 79679654
81267499
4656 5 79666742 84936493 4700 5 79679654
81274512
4657 5 79666742 84943705 4701 5 79679654
81763618
4658 5 79666742 169454950 4702 5 79679654
81797217
4659 5 79666742 181522829 4703 5 79679654
81800186
4660 5 79666742 204759879 4704 5 79679654
81806213
4661 5 79666742 209874191 4705 5 79679654
81854583
4662 5 79679654 79682242 4706 5 79679654
81859374
4463 5 79679654 79699261 4707 5 79679654
81861368
4664 5 79679654 79710673 4708 5 79679654
81863686
4665 5 79679654 79861902 4709 5 79679654
81916850
4666 5 79679654 79867710 4710 5 79679654
81954891
4667 5 79679654 79867868 4711 5 79679654
81985250
4668 5 79679654 79867873 4712 5 79679654
82083752
4669 5 79679654 79961961 4713 5 79679654
82101253
4670 5 79679654 80086268 4714 5 79679654
82143124
4671 5 79679654 80190673 4715 5 79679654
82236318
4672 5 79679654 80190777 4716 5 79679654
82325587
4673 5 79679654 80192546 4717 5 79679654
82427210
4674 5 79679654 80195395 4718 5 79679654
82431853
163
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chouuoson3a1
Segment Chr. Boundary 1 Boundary2 Sqpnent Chn Boundaryl
Boundary 2
4719 5 79679654 82446714 4763 5 79679654
84254208
4720 5 79679654 82446794 4764 5 79679654
84314930
4721 5 79679654 82551111 4765 5 79679654
84340523
4722 5 79679654 82552090 4766 5 79679654
84516340
4723 5 79679654 82555641 4767 5 79679654
04706916
4724 5 79679654 82555670 4768 5 79679654
64799488
4725 5 79679654 82556511 4769 5 79679654
84801081
4726 5 79679654 82559047 4770 5 79679654
84824103
4727 5 79679654 82561535 4771 5 79679654
84824203
4728 5 79679654 82610100 4772 5 79679654
84824816
4729 5 79679654 82676822 4773 5 79679654
84825422
4730 5 79679654 82676901 4774 5 79679654
84825763
4731 5 79679654 82883691 4775 5 79679654
84825942
4732 5 79679654 82954942 4776 5 79679654
84843411
4733 5 79679654 82971688 4777 5 79679654
84936441
. .
=
4734 5 79679654 83023965 4778 5 79679654
84936493
4735 5 79679654 83094205 4779 5 79679654
84943705
4736 5 79679654 83146355 4780 5 79679654
169454950
4737 5 79679654 83280630 4781 5 79679654
181522829
4738 5 79679654 83281412 4782 5 79679654
204759879
4739 5 79679654 83400242 4783 5 79679654
209874191
4740 5 79679654 83405797 4784 5 79697555
79699261
4741 5 79679654 83437132 4785 5 79697555
79710673
4742 5 79679654 83522252 4786 5 79697555
79861902
4743 5 79679654 83560095 4787 5 79697555
79867710
4744 5 79679654 83560204 4788 5 79697555
79867868
4745 5 79679654 83572400 4789 5 79697555
79867873
4746 5 79679654 83607661 4790 5 79697555
79961961
4747 5 79679654 83745342 4791 5 79697555
80086268
4748 5 79679654 83861275 4792 5 79697555
80190673
4749 5 79679654 83861633 4793 5 79697555
80190777
4750 5 79679654 83865653 4794 5 79697555
80192546
4751 5 79679654 83865914 4795 5 79697555
80195395
4752 5 79679654 83865920 4796 5 79697555
80199923
4753 5 79679654 83868010 4797 5 79697555
80241911
4754 5 79679654 84019752 4798 5 79697555
80282785
4755 5 79679654 84065912 4799 5 . 79697555
80345337
4756 5 79679654 84086632 4800 5 79697555
80389787
4757 5 79679654 84089603 4801 5 79697555
80411639
4758 5 79679654 84104814 4802 5 79697555
80446855
4759 5 79679654 84105175 4803 5 79697555
80492790
4760 5 79679654 84251635 4804 5 79697555
80670554
4761 5 79679654 84252180 4805 5 79697555
80674679
4762 5 79679654 84253030 4806 5 79697555
80720509
164
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chunnomunal anomngunal
Segnmnt Chr. Boundary! Boundary2 Segatent Chr. Boundaryl
Boundary2
4807 5 79697555 80800856 4851 5 79697555
82676901
4808 5 79697555 80804587 4852 5 79697555
82883691
4809 5 79697555 80807409 4853 5 79697555
82954942
4810 5 79697555 80835734 . 4854 5 79697555
82971688
41111 5 79697555 80971764 4855 5 79697555
83023965
4612 5 79697555 80972258 4856 5 79697555
83094205
4813 5 79697555 80974450 4857 5 79697555
83146355
4814 5 79697555 81047638 4858 5 79697555
83280630
4815 5 79697555 81082921 4859 5 79697555
83281412
4816 5 79697555 81157909 4860 5 79697555
83400242
- 4817 5 79697555 81265937 4861 5 79697555 83405797
4818 5 79697555 81265937 4862 5 79697555
83437132
4819 5 79697555 01267485 4863 5 79697555
83522252
4820 5 79697555 81267499 4864 5 79697555
83560095
. 4821 5 79697555 81274512 4865 5 79697555
83560204
4822 5 79697555 81763618 4866 5 79697555
83572400
4823 5 79697555 81797217 4867 5 79697555
83607661
4824 5 79697555 81800186 4868 5 79697555
83745342
4825 5 79697555 81806213 4869 5 79697555
83861275
4826 5 79697555 81854583 4870 5 79697555
83861633
4827 5 79697555 81859374 4871 5 79697555
83865653
4828. 5 79697555 81861368 4872 5 79697555
83865914
4829 5 79697555 81863686 4873 5 79697555
83865920
4830 5 79697555 81916850 4874 5 79697555
83868010
4831 5 79697555 81954891 4875 5 79697555
84019752
4832 5 79697555 81985250 4876 5 79697555
84065912
4833 5 79697555 82083752 4877 5 79697555
84086632
4834 5 79697555 82101253 4878 5 79697555
84089603
4835 5 79697555 82143124 4879 5 79697555
84104814
4836 5 79697555 82236318 4880 5 79697555
84105175
4837 5 79697555 82325587 4881 5 79697555
84251635
4838 5 79697555 82427210 4882 5 79697555
84252180
4839 5 79697555 82431853 4883 5 79697555
84253030
4840 5 79697555 82446714 . 4884 5 79697555
84254208
4841 5 79697555 82446794 4885 5 79697555
84314930
4842 5 79697555 82551111 4886 5 79697555
84340523
4843 5 79697555 82552090 4887 5 79697555
84516340
4844 5 79697555 82555641 4888 5 79697555
84706916
4845 5 79697555 82555670 4889 5 79697555
84799488
4846 5 79697555 82556511 4890 5 79697555
84801081 ,
4847 5 79697555 82559047 4891 5 79697555
84824103
4848 5 79697555 82561535 4892 5 79697555
84824203
4849 5 79697555 ' 82610100 4893 5 79697555
84824816
4850 5 79697555 82676822 4894 5 79697555
84825422
165
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Clumnosomal
Segment Chr. Doundary1 Boundmy2 Segment Chn Boundary] Boundary2
4895 5 79697555 84825763 4939 5 79857859
81267499
4896 5 79697555 84825942 4940 5 79857859
81274512
4897 3 79697555 84843411 4941 5 79857859
81763618
4898 5 79697555 84936441 4942 5 79857859
81797217
4899 5 79697555 84936493 4943 5 79857859
81800186
4900 5 79697555 84943705 4944 5 79857859
81806213
4901 5 79697555 169454950 4945 5 79857859
81854583
4902 5 79697555 181522829 4946 5 79857859
81859374
4903 5 79697555 204759879 4947 5 79857859
81861368
4904 5 79697555 209874191 4948 5 79857859
81863686
4905 5 79857859 79861902 4949 5 79857859
81916850
4906 5 79857859 79867710 4950 5 79857859
81954891
4907 5 79857859 79867868 4951 5 79857859
81985250
4908 5 79857859 79867873 4952 5 79857859
82083752
4909 5 79857859 79961961 4953 5 79857859
82101253
4910 5 79857859 80086268 4954 5 79857859
82143124
4911 5 79857859 80190673 4955 5 79857859
82236318
4912 5 74857859 80190777 4956 5 79857859
82325587
4913 5 79857859 80192546 4957 5 79857859
82427210
4914 5 79857859 80195395 4958 5 79857859
82431853
4915 5 79857859 80199923 4959 5 79857859
82446714
4916 5 79857859 80241911 4960 5 79857859
82446794
4917 5 79857859 80282785 4961 5 79857859
82551111
4918 5 79857859 80345337 4962 5 79857859
82552090
=
4919 5 79857859 80389787 4963 5 79857859
82555641
4920 5 79857859 80411639 4964 5 79857859
82555670
4921 5 79857859 80446855 4965 5 79857859
82556511
4922 5 79857859 80492790 4966 5 79857859
82559047
4923 5 79857859 80670554 4967 5 79857859
82561535
4924 5 79857859 80674679 4968 5 79857859
82610100
4925 5 79857859 80720509 4969 5 79857859
82676822
4926 5 79857859 80800856 4970 5 79857859
82676901
4927 5 79857859 80804587 4971 5 79857859
82883691
4928 5 79857859 80807409 4972 5 79857859
82954942
4929 5 79857859 80835734 4973 5 79857859
82971688
4930 5 79857859 80971764 4974 5 79857859
83023965
4931 5 79857859 80972258 4975 5 79857859
83094205
4932 5 79857859 80974450 4976 5 79857859
83146355
4933 5 79857859 81047638 4977 5 79857859
83280630
4934 5 79857859 81082921 4978 5 79857859
83281412
4935 5 79857859 81157909 4979 5 79857859
83400242
4936 5 79857859 81265937 4980 5 79857859
83405797
4937 5 79857859 81265937 4981 5 79857859
83437132
4938 5 79857859 81267485 4982 5 79857859
83522252
166
CA 02 9 3 95 8 0 2 0 16 ¨ 0 8 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundary! Boundmy2 Segment Chr. Boundaryl Boundary2
4983 5 79857859 83560095 5027 5 79862405 79961961
4984 5 79857859 83560204 5028 5 79862405 80086268
4985 5 79857859 83572400 5029 5 79862405 80190673
4986 5 79857859 83607661 5030 5 79862405 80190777
4987 5 79857859 83745342 5031 5 79862405 80192546
4988 5 79857859 83861275 5032 5 79862405 80195395
4989 5 79857859 83861633 5033 5 79862405 80199923
4990 5 79857859 83865653 5034 5 79862405 80241911
4991 5 79857859 83865914 5035 5 79862405 80282785 .
4992 5 79857859 83865920 5036 5 79862405 80345337
4993 5 79857659 83868010 5037 5 79862405 80389787
4994 5 79857859 84019752 5038 5 79862405 80411639
4995 5 79857859 84065912 5039 5 79862405 80446855
4996 5 79857859 64086632 5040 5 79862405 80492790
4997 5 79857859 84089603 5041 5 79862405 80670554
4998 5 79857859 84104814 5042 5 79862405 80674679
4999 5 79857859 84105175 5043 5 79862405 80720509
5000 5 79857859 84251635 5044 5 79862405 80800856
5001 5 79857859 84252180 5045 5 79862405 80004587
5002 5 79857859 84253030 5046 5 79862405 80807409
5003 5 79857859 84254208 5047 5 79862405 80835734
5004 5 79857859 84314930 5048 5 79862405 80971764
5005 5 79857859 84340523 5049 5 79862405 80972258
5006 5 79857859 84516340 5050 5 79862405 80974450
5007 5 79857859 84706916 5051 5 79862405 81047638
5008 5 79857859 84799488 5052 5 79862405 81082921
5009 5 79857859 84801081 5053 5 79862405 81157909
5010 5 79857859 84824103 5054 5 79862405 81265937
5011 5 79857859 84824203 5055 5 79862405 81265937
5012 5 79857859 84824816 5056 5 79862405 81267485
5013 5 79857859 84825422 5057 5 79862405 81267499
5014 5 79857859 84825763 5058 5 79862405 81274512
5015 5 79857859 84825942 5059 5 79862405 81763618
5016 5 79857859 84843411 5060 5 79862405 81797217
5017 5 79857859 84936441 5061 5 79862405 81800186
5018 5 79857859 84936493 5062 5 79862405 81806213
5019 5 79857859 84943705 5063 5 79862405 81854583
5020 5 79857859 169454950 5064 5 79862405 81859374
5021 5 79857859 181522829 5065 5 79862405 81861368
5022 5 79857859 204759879 5066 5 79862405 81863686
5023 5 79857859 209874191 5067 5 79862405 81916850
5024 5 79862405 79867710 5068 5 79862405 81954891
5025 5 79862405 79867868 5069 5 79862405 81985250
5026 5 79862405 79867873 5070 5 79862405 82083752
167
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Oa. Roundary1
Boandary2
5071 5 79862405 82101253 5115 5 79862405
84089603
5072 5 79862405 82143124 5116 5 79862405
84104814
5073 5 79862405 82236318 5117 5 79862405
84105175
5074 5 79862405 82325587 5118 5 79862405
84251635
5075 5 79862405 82427210 5119 5 79862405
84252180
5076 5 79862405 82431853 5120 5 79862405
84253030
5077 5 79862405 82446714 5121 5 79862405
84254208
5078 5 79862405 82446794 5122 5 79862405
14314930
5079 5 79862405 82551111 5123 5 79862405
84340523
5080 5 79862405 82552090 5124 5 79862405
84516340
5081 5 79862405 82555641 5125 5 79862405
84706916
5082 5 79862405 82555670 5126 5 79862405
84799488
5083 5 79862405 82556511 5127 5 79862405
84801081
5084 5 79862405 82559047 5128 5 79862405
84824103
5085 5 79862405 82561535 5129 5 79862405
84824203
5086 5 79862405 82610100 5130 5 79862405
84824816
5087 5 79862405 82676822 5131 5 79862405
84825422
5088 5 79862405 82676901 5132 5 79862405
84125763
5089 5 79062405 02883691 5133 5 79862405
84825942
5090 5 79862405 82954942 5134 5 79862405
84843411
5091 5 79862405 82971686 5135 5 79862405
84936441
5092 5 79862405 83023965 5136 i 79862405
84936493
5093 5 79862405 83094205 5137 5 79862405
84943705
5094 5 79862405 83146355 5138 5 79862405
169454950
5095 5 79862405 83280630 5139 5 79862405
181522829
5096 5 79862405 83281412 5140 5 79862405
204759879
5097 5 79862405 83400242 5141 5 79862405
209874191
5098 5 79862405 83405797 5142 5 79960831
79961961
5099 5 79862405 83437132 5143 5 79960831
80086268
5100 5 79862405 83522252 5144 5 79960831
80190673
5101 5 79862405 83560095 5145 5 79960831
80190777
5102 5 79862405 83560204 5146 ,5 79960831
80192546
5103 5 79862405 83572400 5147 5 79960831
80195395
5104 5 79862405 83607661 5148 5 79960831
80199923
5105 5 79862405 83745342 5149 5 79960831
80241911
5106 5 79862405 83861275 5150 5 79960831
80282785
5107 5 79862405 83861633 5151 5 79960831
80345337
5108 5 79862405 83865653 5152 5 79960831
80389787
5109 5 79862405 83865914 5153 5 79960831
80411639
5110 5 79862405 83865920 . 5154 5 79960831
80446855
5111 5 79862405 83868010 5155 5 79960831
80492790
5112 5 79862405 84019752 5156 5 79960831
80670554
5113 5 79862405 84065912 5157 5 79960831
80674679
5114 5 79862405 84086632 5158 5 79960831
80720509
168
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Boundary 1 Boundary2 Segment Chr 13oundary1
Boundary2
5159 5 79960831 80800856 5203 5 79960831
82676901
5160 5 79960831 80804587 5204 5 79960831
82883691
5161 5 79960831 80807409 5205 5 79960831
82954942
5162 5 79960831 110835734 5206 5 79960831
82971688
5163 5 79960831 80971764 5207 5 79960831
83023965
5164 5 79960831 80972258 5208 5 79960831
83094205
5165 5 79960831 80974450 5209 5 79960831
83146355
5166 5 79960831 81047638 5210 5 79960831
83280630
5167 5 79960831 81082921 5211 5 79960831
83281412
5168 5 79960831 81157909 5212 5 79960831
83400242
5169 5 79960831 81265937 5213 5 79960831
83405797
5170 5 79960831 81265937 5214 5 79960831
83437132
5171 5 79960831 81267485 5215 5 79960831
83522252
5172 5 79960831 81267499 5216 5 79960831
83560095
5173 5 79960831 81274512 5217 5 79960831
83560204
5174 5 79960831 81763618 5218 5 79960831
83572400
5175 5 79960831 81797217 5219 5 79960831
83607661
5176 5 79960831 81800186 5220 5 79960831
83745342
5177 5 79960831 81806213 5221 5 79960831
83861275
5178 5 79960831 81854583 5222 5 79960831
83861633
5179 5 79960831 81859374 5223 5 79960831
83865653
5180 5 79960831 81861368 5224 5 79960831
83065914
5181 5 79960831 81863686 5225 5 79960831
83865920
5182 5 79960831 81916850 5226 5 79960831
83868010
5183 5 79960831 81954891 5227 5 79960831
84019752
5184 5 79960831 81985250 5228 5 79960831
84065912
5185 5 79960831 82083752 5229 5 79960831
84086632
5186 5 79960831 82101253 5230 5 79960831
84089603
5187 5 79960831 82143124 5231 5 79960831
84104814
5188 5 79960831 82236318 5232 5 79960831
84105175
5189 5 79960831 82325587 5233 5 79960031
84251635
5190 5 79960831 82427210 5234 5 79960631
84252180
5191 5 79960831 82431853 5235 5 79960831
84253030
5192 5 79960831 82446714 5236 5 79960831
84254208
5193 5 79960831 82446794 5237 5 79960831
84314930
5194 5 79960831 82551111 5238 5 79960831
84340523
5195 5 79960831 82552090 5239 5 79960831
84516340
5196 5 79960831 82555641 5240 5 79960831
84706916
5197 5 79960831 82555670 5241 5 79960831
84799488
5198 5 79960831 82556511 5242 5 79960831
84801081
5199 5 79960831 82559047 5243 5 79960831
84824103
5200 5 79960831 82561535 5244 5 79960831
84824203
5201 5 79960831 82610100 5245 5 79960831
84824816
5202 5 79960831 82676822 5246 5 79960831
84825422
169
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
=
Table 1 (cont'cl.)
Chromosomal Chromosomal
Somali. CM. Boundmyl Boundary2 Segment Chr Boundary 1
Boundary2
5247 5 79960831 84825763 5291 5 80084956
81806213
5248 5 79960831 84825942 5292 5 80084956
81854583
5249 5 79960831 84843411 5293 5 80084956
81859374
5250 5 79960831 84936441 5294 5 80084956
81861368
5251 5 79960831 84936493 5295 5 80084956
81863686
5252 5 79960831 84943705 5296 5 80084956
81916850
5253 5 79960831 169454950 5297 5 80084956
81954891
5254 5 79960831 181522829 5298 5 80084956
81985250
5255 5 79960831 204759879 5299 5 80084956
82083752
5256 5 79960831 209874191 5300 5 80084956
82101253
5257 5 80084956 80086268 5301 5 80084956
82143124
5258 5 80084956 80190673 5302 5 80084956
82236318
5259 5 80084956 80190777 5303 5 80084956
82325587
5260 5 80084956 80192546 5304 5 80084956
82427210
5261 5 80084956 80195395 5305 5 80084956
82431853
5262 5 80084956 80199923 5306 5 80084956
82446714
5263 5 80084956 80241911 5307 5 80084956
82446794
5264 5 80084956 80282785 5308 5 80084956
82551111
5265 5 80084956 80345337 5309 5 80084956
82552090
5266 5 80084956 80389787 5310 5 80084956
82555641
5267 5 80084956 80411639 5311 5 80084956
82555670
5268 5 80084956 80446855 5312 5 800114956
82556511
5269 5 80384956 80492790 5313 5 80084956
82559047
5270 5 80084956 80670554 5314 5 80084956
82561535
5271 5 80084956 80674679 5315 5 80084956
82610100
5272 5 80084956 80720509 5316 5 80084956
82676822
5273 5 80084956 80800856 5317 5 80084956
82676901
5274 5 80084956 80804587 5318 5 83084956
82883691
5275 5 80084956 80807409 5319 5 80084956
82954942
5276 5 80084956 80835734 5320 5 80084956
82971688
5277 5 80084956 80971764 5321 5 80084956
83023965
5278 5 80084956 80972258 5322 5 80084956
83094205
5279 5 80084956 80974450 5323 5 80084956
83146355
5280 5 80084956 81047638 5324 5 80084956
83280630
5281 5 80084956 81082921 5325 5 80084956
83281412
5282 5 80084956 81157909 5326 5 80084956
83400242
5283 5 80084956 81265937 5327 5 80084956
83405797
5284 5 80084956 81265937 5328 5 80084956
83437132
5285 5 80084956 81267485 5329 5 80084956
83522252
5286 5 80084956 81267499 5330 5 80084956
83560095
5287 5 80084956 81274512 5331 5 80084956
83560204
5288 5 80084956 81763618 5332 5 80084956
83572400
5289 5 80084956 81797217 5333 5 80084956
83607661
5290 5 80084956 81800186 5334 5 80084956
83745342
170
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (coed.)
Chromosomal Chromosomal
Segment (Sr. Boundary]. Boundary2 Segment Chr. Boundary] Boundmy2
5335 5 60084956 83861275 5379 5 80187987
80389787
5336 5 80084956 83861633 5380 5 80187987
80411639
5337 5 80084956 83865653 5381 5 80187987
80446855
5338 5 80084956 513865914 5382 5 80187987
80492790
5339 5 80084956 83865920 5383 5 80187987
80670554
5340 5 80084956 83668010 5384 5 80187987
80674679
5341 5 80084956 84019752 5385 5 80187987
80720509
5342 5 80084956 84065912 5386 5 80187987
80800856
5343 5 80084956 84086632 5387 5 80187987
80804587
5344 5 80084956 84089603 5388 5 80187987
80807409
5345 5 80084956 84104814 5389 5 80187987
80835734
5346 5 80084956 84105175 5390 5 80187987
80971764
5347 5 80084956 84251635 5391 5 80187987
80972258
5348 5 80084956 84252180 5392 5 80187987
80974450
5349 5 80084956 84253030 5393 5 80187987
81047638
5350 5 80084956 84254208 5394 5 80187987
81082921
5351 5 80084956 84314930 5395 5 80187987
81157909
5352 5 80084956 84340523 5396 5 80187987
81265937
5353 5 80084956 84516340 5397 5 80187987
81265937
5354 5 80084956 84706916 ( 5398 5 80187987
81267485
5355 5 80084956 84799488 5399 5 80187987
81267499
5356 5 80084956 84801081 5400 5 80187987
81274512
5357 5 80084956 84824103 5401 5 80187987
81763618
53513 5 80084956 84824203 5402 5 80187987
81797217
5359 5 80084956 84824816 5403 5 80187987
81800186
5360 5 80084956 84825422 5404 5 80187987
81806213
5361 5 80084956 84825763 5405 5 80187987
81854583
5362 5 80084956 84825942 5406 5 80187987
81859374
5363 5 80084956 841341411 5407 5 80187987
81861368
5364 5 80084956 84936441 5408 5 80187987
81863606
5365 5 80084956 84936493 5409 5 80187987
81916850
5366 5 80084956 84943705 5410 5 80187987
81954891
5367 5 80084956 169454950 5411 5 80187987
81985250
5368 5 60084956 181522829 5412 5 80187987
82083752
5369 5 80084956 204759879 5413 5 80187987
82101253
5370 5 80084956 209874191 5414 5 80187987
82143124
5371 5 80187987 80190673 5415 5 80187987
82236318
5372 5 80187987 80190777 5416 5 80187987
82325587
5373 5 80187987 80192546 5417 5 80187987
82427210
5374 5 80187987 80195395 5418 5 80187987
82431853
5375 5 80187987 80199923 5419 5 80187987
82446714
5376 5 80187987 80241911 5420 5 80187987
82446794
5377 5 80187987 80282785 5421 5 80187987
82551111
5378 5 80187987 80345337 5422 5 80187907
82552090
171
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WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chroramormil Chromosomal
Segment Chr. Boundary1 Boundary2 Segment Chr Boundaryl
Boundary 2
5423 5 80187987 82555641 5467 5 80187987
84706916
5424 5 80187987 82555670 5468 5 80187987
84799488
5425 5 80187987 82556511 5469 5 80187987
84801081
5426 5 80187987 82559047 5470 5 80187987
84824103
5427 5 80187987 82561535 5471 5 80187987
84824203
5428 5 80187987 82610100 5472 5 80187987
84824816
5429 5 80187987 82676822 5473 5 80187987
84825422
5430 5 80187987 82676901 5474 5 80187987
84825763
5431 5 80187987 82883691 5475 5 80187987
84825942
5432 5 80187987 82954942 5476 5 80187987
84843411
5433 5 80187987 82971688 5477 5 80187987
84936441
5434 5 80187987 83023965 5478 5 80187987
84936493
5435 5 80187987 83094205 5479 5 80187987
84943705
5436 5 80187987 83146355 5480 5 80187987
169454950
5437 5 80187987 83280630 5481 5 80187987
181522829
5438 5 80187987 83281412 5482 5 80187987
204759879
5439 5 80187987 83400242 5483 5 80187987
209874191
5440 5 80187987 83405797 5484 5 80188978
80190673
5441 5 80187987 83437132 5485 5 80188978
80190777
5412 5 80187987 83522252 5486 5 801104978
80192546
5443 5 80187987 83560095 5487 5 80188978
80195395
5444 5 80187987 83560204 5488 5 80188978
80199923
5445 5 80187987 83572400 5489 5 80188978
80241911
-
5446 5 80187987 83607661 5490 5 80188978
80282785
5447 5 80187987 83745342 5491 5 80188978
80345337
5448 5 80187987 83861275 5492 5 80188978
80389787
5449 5 80187987 83861633 5493 5 80188978
80411639
5450 5 80187987 83865653 5494 5 80188978
80446855
5451 5 80187987 83865914 5495 5 80188978
80492790
5452 5 80187987 83865920 5496 5 80188978
80670554
5453 5 80187987 83868010 5497 5 80188978
80674679
5454 5 80187987 84019752 5498 5 80188978
80720509
5455 5 10187987 84065912 5499 5 80188978
80800856
5456 5 80187987 84086632 5500 5 80188978
80804587
5457 5 80187987 84089603 5501 5 80188978
80807409
5458 5 80187987 84104814 5502 5 80188978
80835734
5459 5 80187987 84105175 5503 5 80188978
80971764
5460 5 80187987 84251635 5504 5 80188978
80972258
5461 5 80187987 84252180 5505 5 80188978
80974450
5462 5 80187987 84253030 5506 5 80188978
81047638
5463 5 80187987 84254208 5507 5 80188978
81082921
5464 5 80187987 84314930 5508 5 80188978
81157909
5465 5 80187987 84340523 5509 5 80188978
81265937
5466 5 80187987 84516340 5510 5 80188978
81265937
'
172
CA 02939580 2016-08-11
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PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment dir. Boundaryl Boundary2 Segment Om Boundary1 Boundary2
5511 , 5 80188978 81267485 5555 5 80188978 83522252
5512 5 80188978 81267499 5556 5 80188978
83560095
5513 5 80188978 81274512 5557 5 80188978
83560204
5514 5 80188978 81763618 5558 5 80188978
83572400
5515 5 80188978 81797217 5559 5 80188978
83607661
5516 5 80188978 81800186 5560 5 80188978
83745342
5517 5 80188978 81806213 5561 5 80188978
83861275
5518 5 80188978 81854583 5562 5 80188978
83861633
5519 5 80188978 81859374 5563 5 80188978
83865653
5520 5 80188978 81861368 5564 5 80188978
83865914
5521 5 80188978 81863686 5565 5 80188978
83865920
5522 5 80188978 01916850 5566 5 80188978
83868010
5523 5 80188978 81954891 5567 5 80188978
84019752
5524 5 80188978 81985250 5568 5 80188978
84065912
5525 5 80188978 82083752 5569 5 80188978
84086632
5526 5 80188978 82101253 5570 5 80188978
84089603
5527 5 80188978 82143124 5571 5 80188978
84104814
5528 5 80188978 82236318 5572 5 80188978
84105175
5529 5 80188978 82325587 5573 5 80188976
84251635
5530 5 80188978 82427210 5574 5 80188978
84252180
5531 5 80188978 82431853 5575 5 80188978
84253030
5532 5 80188978 82446714 5576 5 80188978
84254208
5533 5 80188978 82446794 5577 5 80188978
84314930
5534 5 80188978 82551111 5578 5 80188978
84340523
5535 5 80188978 82552090 5579 5 80188978
84516340
5536 5 80188978 82555641 5580 5 80188978
84706916
5537 5 80188978 82555670 5581 5 80188978
84799488
5538 5 80188978 82556511 5582 5 80188978
84801081
5539 5 80188978 82559047 5583 5 80188978
84824103
5540 5 80188978 82561535 5584 5 80188978
84124203
5541 5 80188978 82610100 5585 5 80188978
84824816
5542 5 80188978 82676822 5586 5 80188978
84825422
5543 5 80188978 82676901 5587 5 80188978
84825763
5544 5 80188978 82883691 5588 5 80188978
84825942
5545 5 80188978 82954942 5589 5 80188978
84843411
5546 5 80188978 82971688 5590 5 80188978
84936441
5547 5 80188978 83023965 5591 5 80188978
84936493
5548 5 80188978 83094205 5592 5 80188978
84943705
5549 5 80188978 83146355 5593 5 80188978
169454950
5550 5 80188978 83280630 5594 5 80188978
181522829
.
5551 5 80188978 83281412 5595 5 80108978
204759879
5552 5 80188978 83400242 5596 5 80188978
209874191
5553 5 80188978 63405797 5597 5 80191781
80192546
5554 5 80188978 83437132 5598 5 80191781
80195395
173
CA 02939580 2016-08-11
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PCT/US2015/016877
'
Table 1 (contd.)
Chromosomal Chnnnosthmal
Segnent Cho. Boundary]. Boundary2 Sagnent Cht Boundary1
Boundary 2
5599 5 80191781 80199923 5643 5 80191781
82446714
5600 5 80191781 80241911 5644 5 80191781
82446794
5601 5 80191781 80282785 5645 5 80191781
82551111
5602 5 80191781 80345337 5646 5 80191781
82552090
5603 5 80191781 80389787 5647 5 80191781
62555641
5604 5 80191781 80411639 5648 5 80191781
82555670
5605 5 80191781 80446855 5649 5 80191781
82556511
5606 5 80191781 80492790 5650 5 80191781
82559047
5607 5 80191781 80670554 5651 5 80191781
82561535
5608 5 80191781 80674679 5652 5 80191781
82610100
5609 5 80191781 80720509 5653 5 80191781
82676822
5610 5 80191781 80800856 5654 5 80191781
82676901
5611 5 80191781 80804587 5655 5 80191781
82883691
5612 5 80191781 80807409 5656 5 80191781
82954942
5613 5 80191781 80835734 5657 5 80191781
82971688
5614 5 80191781 80971764 5658 5 80191781
83023965
5615 5 80191781 80972258 5659 5 80191781
83094205
5616 5 80191781 80974450 5660 5 80191781
83146355
5617 5 80191781 81047638 5661 5 80191781
83280630
5618 5 80191781 81082921 5662 5 80191781
83281412
5619 5 80191781 81157909 5663 5 80191781
83400242
5620 5 80191781 81265937 5664 5 80191781
83405797
5621 5 80191781 81265937 5665 5 80191781
83437132
5622 5 80191781 81267485 5666 5 80191781
83522252
5623 5 80191781 81267499 5667 5 80191781
83560095
5624 5 80191781 81274512 5668 5 80191781
83560204
5625 5 80191781 81763618 5669 5 80191781
83572400
5626 5 80191781 81797217 5670 5 80191781
83607661
5627 5 80191781 81800186 5671 5 80191781
83745342
5628 5 80191781 81806213 5672 5 80191781
83861275
5629 5 80191781 81854583 5673 5 80191781
83861633
5630 5 80191781 81859374 5674 5 80191781
83865653
5631 5 80191781 81861368 5675 5 80191781
83865914
5632 5 80191781 81863686 5676 5 80191781
83865920
5633 5 80191781 81916850 5677 5 80191781
83868010
5634 5 80191781 81954891 5678 5 80191781
84019752
5635 5 80191781 81985250 5679 5 80191781
84065912
5636 5 80191781 82083752 5680 5 80191781
84086632
9637 5 80191781 82101253 5681 5 80191781
84089603
5638 5 80191781 82143124 5682 5 80191781
84104814
5639 5 80191781 82236318 5683 5 80191781
84105175
5640 5 80191781 82325587 5684 5 80191781
84251635
5641 5 80191781 82427210 5685 5 80191781
84252180
5642 5 80191781 ' 82431853 5686 5 80191781 84253030
174
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PCT/US2015/016877
Table 1 (contd.)
Chromosomal Clumnosmnal
Segment Chr. Boundary1 Boundary2 Segment Chr. Boundary1 Boundary2
5687 5 80191781 84254208 5731 5 80195077
81265937
5688 5 80191781 84314930 5732 5 80195077
81267485
5689 5 80191781 84340523 5733 5 80195077
81267499
5690 5 80191781 84516340 5734 5 80195077
81274512
5691 5 80191781 84706916 5735 5 80195077
81763618
5692 5 80191781 84799488 5776 5 80195077
81797217
5693 5 80191781 84801081 5737 5 80195077
81800186
5694 5 80191781 84824103 5778 5 80195077
81806213
5695 5 80191781 84824203 5739 5 80195077
81854583
5696 5 80191781 84824816 5740 5 80195077
81859374
5697 5 80191781 84825422 5741 5 80195077
81861368
5698 5 80191781 84825767 5742 5 80195077
81863686
5699 5 80191781 84825942 5743 5 80195077
81916850
5700 5 80191781 84843411 5744 5 80195077
81954891
5701 5 80191781 84936441 5745 5 80195077
81985250
5702 5 80191781 84936493 5746 5 80195077
82083752
5703 5 80191781 84943705 5747 5 80195077
82101253
5704 5 80191781 169454950 5748 5 80195077
82143124
5705 5 80191781 181522829 5749 5 80195077
82236318
5706 5 80191781 204759879 5750 5 80195077
82325587
5707 5 80191781 209874191 5751 5 80195077
82427210
5708 5 80195077 80195395 5752 5 80195077
82471857
5709 5 80195077 80199923 5753 5 80195077
82446714
5710 5 80195077 80241911 5754 5 80195077
82446794
5711 5 80195077 80282785 5755 5 80195077
82551111
5712 5 80195077 80745777 5756 5 80195077
82552090
5713 5 80195077 80389787 5757 5 80195077
82555641
5714 5 80195077 80411639 5758 5 80195077
82555670
5715 5 80195077 80446855 5759 5 80195077
82556511
5716 5 80195077 80492790 5760 5 80195077
82559047
5717 5 80195077 80670554 5761 5 80195077
82561535
5718 5 80195077 80671679 5762 5 80195077
82610100
5719 5 80195077 80720509 5763 5 80195077
82676822
5720 5 80195077 80800856 5764 5 80195077
82676901
5721 5 80195077 80804587 5765 5 80195077
82883691
5722 5 80195077 80807409 5766 5 80195077
82954942
5723 5 80195077 80835734 5767 5 80195077
82971688
5724 5 80195077 80971764 5768 5 80195077
83023965
5725 5 80195077 80972258 5769 5 80195077
83094205
5726 5 80195077 80974450 5770 5 80195077
83146355
5727 5 80195077 81047638 5771 5 80195077
83280630
5728 5 80195077 81082921 5772 5 80195077
83281412
5729 5 80195077 81157909 5773 5 80195077
83400242
5730 5 80195077 81265937 5774 5 80195077
87405797
175
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
'
Table 1 (cont'd.)
Chromosomal Chnmnosonml
Segment Chr. Boundary1 Boundary2 Segment Chu. Bmindanj1 Boundary2
5775 5 80195077 83437132 = 5819 5 80195395 80241911
5776 5 80195077 83522252 5820 5 80195395 80282785
5777 5 80195077 83560095 5821 5 80195395 80345337
5778 5 80195077 83560204 5822 5 80195395 80389787
5779 5 80195077 83572400 5823 5 80195395 80411639
5780 5 80195077 83607661 5824 5 80195395 80446855
5781 5 8.0195077 83745342 5825 5 80195395 80492790
5782 5 80195077 83861275 5826 5 80195395 80670554
5783 5 80195077 83861631 5827 5 80195395 80674679
5784 5 80195077 83865653 5828 5 80195395 80720509
' 5785 5 80195077 83865914 5829 5 80195395 80800856
5786 5 80195077 83865920 5830 5 80195395 80804587
5787 5 80195077 83868010 5831 5 80195395 80807409
5788 5 80195077 84019752 5832 5 80195395 80835734
5789 5 80195077 84065912 5833 5 80195395 80971764
5790 5 80195071 84086632 5834 5 80195395 80972258
5791 5 80195077 84089603 5835 5 80195395 80974450
5792 5 80195077 84104814 5836 5 80195395 81047638
5793 5 80195077 84105175 5837 5 80195395 81082921
5794 5 80195077 84251635 5838 5 80195395 81157909
5795 5 80195077 84252180 5839 5 80195395 81265937
5796 5 80195077 84253030 5140 5 80195395 81265937
5797 5 60195077 84254208 5841 5 80195395 81267485
5798 5 80195077 84314930 5842 5 80195395 81267499
5799 5 80195077 84340523 5843 5 80195595 81274512
5800 5 80195077 , 84516340 5841 5 80195395 81763618
5801 5 80195077 84706916 5845 5 80195395 81797217
5802 5 80195077 84799488 5046 5 80195595 81800186
5803 5 00195077 84801081 5847 5 80195395 81806213
5804 5 80195077 84824103 5848 5 80195395 81854583
5805 5 80195077 84824203 5849 5 80195595 81859374
5806 5 80195077 84824816 5850 5 80195395 81861368
5807 5 80195077 84825422 5851 5 80195395 81863686
5808 5 80195077 84825763 5852 5 80195395 81916850
5809 5 80195077 84825942 5853 5 80195395 81954891
5810 5 80195077 84843411 5854 5 80195395 81985250
5811 5 80195077 84936441 5855 5 80195395 82083752
5812 5 80195077 84936493 5856 5 80195395 82101253
5813 5 80195077 84943705 5857 . 5 80195595 82143124
5814 5 80195077 169454990 5858 5 80195395 82236318
5815 5 80195077 181522829 5859 5 80195395 82325587 .
5816 5 80195077 204759879 5860 5 80195395 82427210
5817 5 80195077 209874191 5861 5 80195395 82431853
5818 5 80195395 80199923 5862 5 80195395 82446714
176
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundary1 Bomadmy2 Segment Cht Boundaryl
Boundary 2
5863 5 80195395 82446794 5907 5 80195395 84314930
5864 5 80195395 82551111 5908 5 80195395 84340523
5665 5 80195395 82552090 5909 5 80195395 84516340
5866 5 80195395 82555641 5910 5 80195395 84706916
5867 5 80195395 82555670 5911 5 80195395 84799488
5868 5 80195395 82556511 5912 5 80195395 84801081
5869 5 80195395 82559047 5913 5 80195395 84824103
5870 5 80195395 82561535 5914 5 80195395 84824201
5871 5 80195395 82610100 5915 5 80195395 84824816
5872 5 80195395 82676822 5916 5 80195395 84825422
5873 5 80195395 . 82676901 5917 5 80195395 84825763
5874 5 80195395 82883691 5918 5 80195395 84825942
5875 5 80195195 82954942 5919 5 80195395 84843411
5876 5 80195395 82971688 5920 5 80195395 84936441
5877 5 80195395 81023965 5921 5 80195395 84936493
5878 5 80195395 83094205 5922 5 80195395 84943705
5879 5 80195395 83146355 5923 5 80195195 169454950
5880 5 80195195 83280630 5924 5 80195395 181522829
5881 5 80195395 83281412 5925 5 80195395 204759879
5882 5 80195395 83400242 5926 5 80195395 209874191
5883 5 80195395 83405797 5927 5 80195714 80199923
5884 5 80195395 83437132 5928 5 80195714 80241911
5885 5 80195395 83522252 5929 5 80195714 80282785
5886 5 80195395 83560095 5930 5 80195714 80345337
5887 5 80195395 83560204 5931 5 80195714 80389787
5888 5 80195395 83572400 5932 5 80195714 80411639
5889 5 80195395 83607661 5933 5 80195714 80446855
,
5890 5 80195395 83745342 5934 5 80195714 80492790
5891 5 80195395 83861275 5915 5 80195714 80670554 =
5892 5 80195395 83861633 5936 5 80195714 80674679
5893 5 80195395 83865653 5937 5 80195714 80720509
5894 5 80195395 83865914 5938 5 80195714 80800856
5895 5 80195395 83865920 5939 5 80195714 80804587
5896 5 80195395 83868010 5940 = 5 80195714 80807409
5897 5 80195395 84019752 5941 5 80195714 80835734
5898 5 80195395 84065912 5942 5 80195714 80971764
5899 5 80195395 84086632 5943 5 80195714 80972256
5900 5 80195395 84089603 5944 5 80195714 80974450
5901 5 80195395 84104814 5945 5 80195714 81047638
5902 5 80195395 84105175 5946 5 80195714 81082921
5903 5 80195395 84251635 5947 5 80195714 81157909
5904 5 80195395 84252180 5948 5 80195714 81265937
5905 5 80195395 84253030 5949 9 80195714 81265937
5906 5 80195395 84254208 5950 5 80195714 81267485
177
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chnunosmnal
Segment Chr, Boundary 1 Boundary 2 Segment Chn Boundary]
Boundary 2
5951 5 80195714 81267499 5995 5 80195714 83560095
5952 5 80195714 81274512 5996 5 80195714 83560204
5953 5 80195714 81763618 5997 5 80195714 83572400
5954 5 80195714 81797217 5998 5 80195714 83607661
5955 5 80195714 81800186 5999 5 80195714 83745342
5956 5 80195714 81806213 6000 5 80195714 83861275
5957 5 80195714 81854583 6001 5 80195714 83861633
5958 5 80195714 81859374 6002 5 80195714 83865653
5959 5 80195714 81861368 6003 5 80195714 83865914
5960 5 80195714 81863686 6004 5 80195714 83865920
5961 5 80195714 81916850 6005 5 80195714 83868010
5962 5 80195714. 81954891 6006 5 80195714 84019752
5963 5 80195714 81985250 6007 5 80195714 84065912
5964 5 80195714 82083752 6008 5 80195714 04086632
5965 5 80195714 = 82101253 6009 5 80195714 84089603
5966 5 80195714 82143124 6010 5 80195714 84104814
5967 5 80195714 82236318 6011 5 80195714 84105175
5968 5 80195714 82325587 6012 5 80195714 84251635
5969 5 80195714 82427210 6013 5 80195714 84252180
5970 5 80195714 82431853 6014 5 80195714 84253030
5971 5 80195714 82446714 6015 5 80195714 84254208
5972 5 80195714 82446794 6016 5 80195714 84314930
5973 5 80195714 82551111 6017 5 80195714 84340523
5974 5 80195714 82552090 6018 5 80195714 84516340
5975 5 80195714 82555641 6019 5 80195714 84706916
5976 5 80195714 82555670 6020 5 80195714 84799488
5977 5 80195714 82556511 6021 5 80195714 84801081
5978 5 80195714 82559047 6022 5 80195714 84824103
5979 5 80195714 82561535 6023 5 80195714 84824203
5980 5 80195714 82610100 6024 5 80195714 84824816
5981 5 80195714 82676822 6025 5 80195714 84825422
5982 5 80195714 82676901 6026 5 80195714 84825763
5983 5 80195714 82883691 6027 5 80195714 84825942
5984 5 80195714 82954942 6028 5 80195714 84843411
5985 5 80195714 82971688 6029 5 80195714 84936441
5986 5 80195714 83023965 6030 5 80195714 84936493
5987 5 80195714 83094205 6031 5 80195714 84943705
5988 5 80195714 83146355 6032 5 80195714 169454950
5989 5 80195714 83280630 6033 5 80195714 181522829
5990 5 80195714 83281412 6034 5 80195714 204759879
5991 5 80195714 83400242 6035 5 80195714 209874191
5992 5 80195714 83405797 6036 5 80236478 80241911
5993 5 80195714 83437132 6037 5 80236478 80282785
5994 5 80195714 83522252 6038 5 80236478 80345337
178
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundaryl Boundary2 Segment Clr.
Boundary 1 Boundary2
6039 5 80236478 80389787 6063 5 80236478
82555641
6040 5 80236478 80411639 6084 5 80236478
82555670
6041 5 80236478 80446855 6085 5 80236478
82556511
6042 5 80236478 80492790 6086 5 80236478
82559047
6043 5 80236478 80670554 6087 5 80236478
82561535
6044 5 80236478 80674679 6088 5 80236478
82610100
6045 5 80236478 80720509 6089 5 80236478
82676822
6046 5 80236478 80800856 6090 5 80236478
82676901
6047 5 80236478 80804587 6091 5 80236478
82883691
6048 5 80236478 80807409 6092 5 80236478
82954942
6049 5 80236478 80835734 6093 5 80236478
82971688
6050 5 80236478 80971764 6094 5 . 80236478
83023965
6051 5 80236478 80972258 6095 5 80236478
83094205
6052 5 80236478 80974450 6096 5 80236478
83146355
6053 5 80236478 81047638 6097 5 80236478
83280620
6054 5 80236478 81082921 6098 5 80226478
83281412
6055 5 80236478 81157909 6099 5 80236478
83400242
6056 5 80236478 81265937 6100 5 80236478
83405797
6057 5 80236478 81265937 6101 5 80236478
83437132
6058 5 80236478 81267485 6102 5 80236478
83522252
6059 5 80236478 81267499 6103 5 80236478
83560095
6060 5 80236478 81274512 6104 5 80236478
83560204
6061 5 80236478 81763618 6105 5 80236478
83572400
6062 5 80236478 81797217 6106 5 80236478
83607661
6063 5 80236478 81800186 0,107 5 80236478
83745342
,
6064 5 80236478 81806213 6108 5 80236478
83861275
6065 5 80236478 81854583 6109 5 80236478
83861633
6066 5. 80236478 81859374 6110 5 80236478
83865653
6067 5 80236478 81861368 6111 5 80236478
83865914
6068 5 80236478 81863686 6112 5 80236478
83865920
6069 5 80236478 81916850 6113 5 80236478
83868010
6070 5 80236478 81954891 6114 5 80236478
84019752
6071 5 80236478 81985250 6115 5 80236478
84065912
6072 5 80236478 82083752 6116 5 80236478
84086632
6073 5 80236478 82101253 6117 5 80236478
84089603
6074 5 80236478 82143124 6118 5 80236478
84104814
6075 5 80236478 82236318 6119 5 80236478
84105175
6076 5 80236478 82325587 6120 5 80236478
84251635
6077 5 80236478 82427210 6121 5 80236478
84252180
6078 5 80236478 82431853 6122 5 80236478
84253030
6079 5 80236478 82446714 6123 5 80236478
84254208
6080 5 80236478 82446794 6124 5 80236478
84314930
6081 5 80236478 82551111 6125 5 80236478
84340523
6082 5 80236478 82552090 6126 5 80236478
84516340
179
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chnsmosonall Chromosomal
Segment. Chr. Boundary1 Boundary2 Segment Chr. Boundary
1 Boundary2
6127 5 80236478 84706916 6171 5 80238986
81800186
6128 5 80236478 84799488 6172 5 80238986
81806213
6129 5 80236478 84801081 6173 5 80238986
81854583
6130 5 80236478 84824103 6174 5 80238986
81859374
6131 5 80236478 84824203 6175 5 80238986
81861368
6132 5 80236478 84824816 6176 5 80238986
81863686
6133 5 80236478 84825422 6177 5 80238986
81916850
6134 5 80236478 84825763 6178 5 80238986
81954891
6135 5 80236478 84825942 6179 5 80238986
81985250
6136 5 80236476 84843411 6180 5 80238986
82083752
6137 5 80236478 84936441 6181 5 80238966
82101253
6138 5 80236478 84936493 6182 5 80238986
82143124
6139 5 80236478 84943705 6183 5 80238986
82236318
6140 5 80236478 169454950 6184 5 80238986
82325587
6141 5 80236478 181522829 6185 5 80238986
82427210
6142 5 80236478 204759879 6186 5 80238986
82431853
6143 5 80236478 209874191 6187 5 80238986
82446714
6144 5 80238966 80241911 6188 5 80238986
82446794
6145 5 80238986 80282785 6189 5 80238986
82551111
6146 5 80238986 80345337 6190 5 80238986
82552090
6147 5 80238986 80389787 6191 5 80238986
82555641
6148 5 80238986 80411639 6192 5 80238986
82555670
6149 5 80238986 80446855 6193 5 80238986
82556511
6150 5 80238986 80492790 6194 5 80238986
82559047
6151 5 80238986 80670554 6195 5 80238986
82561535
6152 5 80238986 80674679 6196 5 80238986
82610100
6153 5 80238986 80720509 6197 5 80238986
82676822
6154 5 80238986 80800856 6198 5 80238986
82676901
6155 5 80238986 80804587 6199 5 80238986
82883691
6156 5 80238986 80807409 6200 5 80238986
82954942
6157 5 80238986 80835734 6201 5 80238986
82971688
6158 5 80238986 80971764 6202 5 80238986
83023965
6159 5 80238986 80972258 6203 5 80238986
83094205
6160 5 80238986 80974450 6204 5 80238986
63146355
6161 5 80238986 8104763/1 6205 5 80238986
83280630
6162 5 80238986 81082921 6206 5 80238986
83281412
6163 5 80238986 81157909 6207 5 80238986
83400242
6161 5 80238986 81265937 6208 5 80238986
83405797
6165 5 80238986 81265937 6209 5 80238986
83437132
6166 5 80238986 81267485 6210 5 80238986
83522252
6167 5 80238986 81267499 6211 5 80238986
83560095
6168 5 80238986 81274512 6212 5 80238986
83560204
6169 5 80238986 81763618 6213 5 80238986
83572400
6170 5 80238986 81797217 6214 5 80238986
83607661
180
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal ChnunosonW
Segment Chu Boundmy1 Boundary2 Segment Chu Boundmy 1
BounMr32
6215 5 80238986 83745342 6259 5 80239243
80670554
6216 5 80238986 83861275 6260 5 80239243
80674679
6217 5 80238986 83861633 6261 5 80239243
80720509
6218 5 80238986 83865653 6262 5 80239243
80800856
6219 5 80238986 83865914 6263 5 80239243
80804587
6220 5 80238986 83865920 6264 5 80239243
80807409
6221 5 80218986 83868010 6265 5 80239243
80835734
6222 5 80238986 84019752 6266 5 80239243
80971764
6223 5 80238986 84065912 6267 5 80239243
80972258
6224 5 80238986 84086632 6268 5 80239243
80974450
6225 5 80238986 84089603 6269 5 80239243
81047638
6226 5 80238986 84104814 6270 5 80239243
81082921
6227 5 80238986 84105175 6271 5 80239243
81157909
6228 5 80238986 84251635 6272 5 80239243
81265937
6229 5 80238986 64252180 6273 5 80239243
81265937
6230 5 80238986 84253030 6274 5 80239243
81267485
6231 5 80238986 84254208 6275 5 80239243
81267499
6232 5 80238986 84314930 6276 5 80239243
81274512
6233 5 80238986 84340523 6277 5 80239243
81763618
6234 5 80238986 84516340 6276 5 80239243
81797217
6235 5 80238986 84706916 6279 5 80239243
81800186
6236 5 80238986 84799488 6280 5 80239243
81806213
6237 5 80238986 84801081 6281 5 80239243
81854583
6238 5 80238986 84824103 6282 5 80239243
81659374
6239 5 80238986 84824203 6283 5 80239243
81861368
6240 5 80238986 84824816 6284 5 80239243
81863686
6241 3 80238986 84825422 6285 5 80239243
81916850
6242 5 80238986 84825763 6286 5 80239243
81954891
6243 5 80238986 84825942 6287 5 80239243
81985250
6244 5 80238986 84843411 6288 5 80239243
82083752
6245 5 80238986 84936441 6289 5 80239243
82101253
6246 5 80238986 84936493 6290 5 80239243
82143124
6247 5 80238986 84943705 6291 5 80239243
82236318
6248 5 80238986 169454950 6292 5 80239243
82325587
6249 5 80238986 181522829 6293 5 80239243
82427210
6250 5 80238986 204759879 6294 5 80239243
82431853
6251 5 80238986 209874191 6295 5 80239243
82446714
6252 5 80239243 80241911 6296 5 80239243
82446794
6253 5 80239243 80282785 6297 5 80239243
82551111
6254 5 80239243 80345337 6298 5 80239243
82552090
6255 5 80239243 80389787 6299 5 80239243
82555641
6256 5 80239243 80411639 6300 5 80239243
82555670
6257 5 80239243 80446855 6301 5 80239243
82556511
6258 5 80239243 80492790 6302 5 80239243
82559047
181 .
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.) ,
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chn Boundary 1
Boundary2
6303 5 80239243 82561535 6347 5 80239243
84824203
6304 5 80239243 82610100 6348 5 80239243
84824816
6305 5 80239243 82676822 6349 5 80239243
84825422
6306 5 80239243 82676901 6350 5 80239243
84825763
6307 5 80239243 82883691 6351 5 80239243
84825942
6308 5 80239243 82954942 6352 5 80239243
84843411
6309 5 80239243 82971688 6353 5 80239243
84936441
6310 5 80239243 83023965 6354 5 80239243
84936493
6311 5 80239243 83094205 6355 5 80239243
84943705
6312 5 80239243 83146355 6356 5 00239243
169454950
6313 5 80239243 83280630 6357 5 80239243
181522829
6314 5 80239243 83281412 6358 5 80239243
204759879
6315 = 5 80239243 83400242 6359 5 80239243 209874191
6316 5 80239243 83405797 6360 5 80273499
80282785
6317 5 80239243 83437132 6361 5 80273499
80345337
6318 5 80239243 83522252 6362 5 80273499
80389787
6319 5 80239243 83560095 6363 5 80273499
80411639
6320 5 80239243 83560204 6364 5 80273499
80446855
6321 5 80239243 83572400 6365 5 80273499
80492790
6322 5 80239243 83607661 6366 5 80273499
80670554
6323 5 80239243 83745342 6367 5 80273499 80674679 .
6324 5 80239243 83861275 6368 5 80273499
80720509
6325 5 80239243 83861633 6369 5 80273499
80000856
6326 5 80239243 83865653 6370 5 80273499
80804587
6327 5 80239243 83865914 6371 5 80273499
80807409
6328 5 80239243 83865920 6372 5 80273499
80835734
6329 5 80239243 83868010 6373 5 80273499
80971764
6330 5 80239243 84019752 6374 5 80273499
80972258
6331 5 80239243 84065912 6375 5 80273499
80974450
6332 5 80239243 84086632 6376 5 80273499
81047638
6333 5 80239243 84089603 6377 5 80273499
81082921
6334 5 80239243 84104814 6378 5 80273499
81157909
6335 5 80239243 84105175 6379 5 80273499
81265937
6336 5 80239243 84251635 6380 5 80273499
81265937
6337 5 80239243 84252180 6381 5 80273499
81267485
6338 5 80239243 84253030 6382 5 80273499
81267499
6339 5 80239243 84254208 6383 5 80273499
81274512
6340 5 80239243 84314930 6384 5 80273499
81763618
6341 5 80239243 84340523 6385 5 80273499
81797217
6342 5 80239243 84516340 6386 5 80273499
81800186
6343 5 80239243 84706916 6387 5 80273499
81806213
6344 5 80239243 84799488 6338 5 80273499
81854583
6345 5 80239243 84801081 6389 ' 5 80273499
81859374
6346 5 80239243 84824103 6390 5 80273499
81861368
182
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
,
Table 1 (contd.)
Chromosomal Clumnosmnal
Segment Chr. Enmndary1 Boundmy2 Segment Chn Boundary]
Boundary 2
6391 5 80273499 81863686 6435 5 80273499
83865920
6392 5 80273499 81916850 6436 5 80273499
83868010
6393 5 80273499 81954891 6437 5 80273499
84019752
6394 5 80273499 81985250 6438 5 80273499
84065912
6395 5 80273499 82083752 6439 5 80271499
84086632
6396 5 80273499 82101253 6440 5 80273499
84089603
6397 5 80273499 82143124 6441 5 80273499
84104814
6398 5 80273499 82236318 6442 5 80273499
84105175
6399 5 80273499 82325587 6443 5 80273499
84251635
6400 5 80273499 82427210 6444 5 80273499
84252180
6401 5 80273499 82431853 6445 5 80273499
84253030
6402 5 80273499 82446714 6446 5 80273499
84254208
6453 5 80273499 82446794 6447 5 80273499
84314930
6404 5 80273499 82551111 6448 5 80273499
84340523
6405 5 80273499 82552090 6449 5 80273499
84516340
6406 5 80273499 82555641 6450 5 80273499
84706916
6407 5 80273499 82555670 6451 5 80273499
84799488
6408 5 80273499 82556511 6452 5 80273499
84801081
6409 5 80273499 82559047 6453 5 80273499
84824103
6410 5 80273499 82561535 6454 5 80273499
84824203
6411 5 60273499 82610100 6455 5 80273499
84824816
6412 5 80273499 82676822 6456 5 80273499
84825422
6413 5 80273499 82676901 6457 5 80273499
84825763
6414 5 80273499 82883691 6458 5 80273499
84825942
6415 5 80273499 82954942 6459 5 80273499
84843411
6416 5 80273499 82971688 6460 5 80273499
84936441
6417 5 80273499 83023965 6461 5 80273499
84936493
' 6418 5 80273499 83094205 6462 5 80273499
84943705
6419 5 80273499 83146359 6463 5 80273499
169454950
6420 5 80273499 83280630 6464 5 80273499
181522829
6421 5 80273499 83281412 6465 9 80273499
204759879
6422 5 80273499 83400242 6.466 5 80273499
209874191
6423 5 80273499 83405797 6467 5 80344025
80349337
6424 5 80273499 83437132 6468 5 80344025
80389787
6425 5 80273499 83522252 6469 5 80344025
80411639
6426 5 80273499 83560095 6470 5 80344025
80446855
6427 5 80273499 83560204 6471 5 80344025
80492790
6428 5 80273499 83572400 6472 5 80344025
80670554
6429 5 80273499 83607661 6473 5 80344029
80674679
6430 5 80273499 83745342 6474 5 80344025
80720509
6431 5 80273499 83861275 6475 5 80344025
80800856
6432 5 80273499 83861633 6476 5 80344025
80804587
6433 5 80273499 83865653 6477 5 80344025
80807409
6434 5 80273499 83865914 6478 5 80344025
80835734
183
CA 02 9 3 95 8 0 2 016 ¨08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (contd.)
Claranosornal Chromosomal
Segment Chn Boundary1 Boundary2 Segment Chn Boundary]. Boundary2
6479 5 80344025 80971764 6523 5 80344025
83023965
6480 5 80344025 80972258 6524 5 80344025
83094205
6481 5 80344025 80974450 6525 5 80344025
83146355
6482 5 80344025 81047638 6526 5 80344025
83280630
6483 5 80344025 81082921 6527 5 80344025
83281412
6484 5 80344025 81157909 6528 5 80344025
83400242
6485 5 80344025 81265937 6529 5 80344025
83405797
6486 5 80344025 81265937 6530 5 80344025
83437132
6487 5 80344025 81267485 6531 5 80344025
83522252
6488 5 80344025 81267499 6532 5 80344025
83560095
6489 5 80344025 81274512 6533 5 80344025
83560204
6490 5 80344025 81763618 6534 5 80344025
83572400
6491 5 80344025 81797217 6535 5 80344025
83607661
6492 5 80344025 81800186 6536 5 80344025
83745342
6493 5 80344025 81806213 6537 5 80344025
83861275
6494 5 80344025 81854583 6538 5 80344025
83861633
6495 5 80344025 81859374 6539 5 80344025
83865653
6496 5 80344025 81861368 6540 5 80344025
83865914
6497 5 80344025 81863686 6541 5 80344025
83865920
6498 5 80344025 81916850 6542 5 80344025
83868010
6459 5 80344025 81954891 6543 5 80344025
84019752
6500 5 80344025 81985250 6544 5 80344025
84065912
6501 5 80344025 82083752 6545 5 80344025
84086632
6502 5 80344025 82101253 6546 5 80344025
84089603
6503 5 80344025 82143124 6547 5 80344025
84104814
6504 5 80344025 82236318 6548 5 80344025
84105175
6505 5 80344025 82325587 6549 5 80344025
84251635
6506 5 80344025 82427210 6550 5 80344025
84252180
6507 5 80344025 82431853 6551 5 80344025
84253030
6508 5 80344025 82446714 6552 5 80344025
84254208
6509 5 80344025 132446794 6553 5 80344025
84314930
6510 5 80344025 82551111 6554 5 80344025
84340523
6511 5 80344025 82552090 6555 5 80344025
84516340
6512 5 80344025 82555641 6556 5 80344025
84706916
6513 5 80344025 82555670 6557 5 80344025
84799488
6514 5 80344025 82556511 6558 5 80344025
84801081
6515 5 80344025 82559047 6559 5 80344025
84824103
6516 5 80344025 82561535 6560 5 80344025
84824203
6517 5 80344025 82610100 6561 5 80344025
84824816
0518 5 80344025 82676822 6562 5 80344025
84825422
6519 5 80344025 82676901 6563 5 80344025
84825763
6520 5 80344025 82883691 6564 5 80344025
84825942
6521 5 80344025 82954942 6565 5 80344025
84843411
6522 5 80344025 82971688 6566 5 80344025
84936441
184
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chnhnomnna
Segment Chr. Boundary1 Boundary2 Segment Chr. Boundary 1
Boundary 2
6567 5 80344025 84936493 6611 5 80387639
82427210
6568 5 80344025 84943705 6612 5 80387639
82431853
6569 5 80344025 169454950 6613 5 80387639
82446714
6570 5 80344025 181522829 6614 5 80387639
82446794
6571 5 80344025 204759879 6615 5 80387639
82551111
6572 5 80344025 209874191 6616 5 80387639
82552090
6573 5 80387639 80389787 6617 5 80387639
82555641
6574 5 80387639 80411639 6618 5 80387639
82555670
6575 5 80387639 80446855 6619 5 80387639
82556511
6576 5 80187639 80492790 6620 5 80387639
82559047
6577 5 80387639 80670554 6621 5 80387639
82561535
6578 5 80387639 80674679 6622 5 80387639
82610100
6579 5 80387639 80720509 6623 5 80387639
82676822
6580 5 80387639 80800856 6624 5 80387639
82676901
6581 5 80387639 80804587 6625 5 80387639
82883691
6582 5 80387639 80807409 6626 5 80387639
82954942
6583 5 80387639 80835734 6627 5 80187639
82971688
6584 5 80387639 80971764 6628 5 80387639
83023965
6585 5 80387639 80972258 6629 5 80387639
83094205
6586 5 80387639 80974450 6630 5 80387639
83146355
6587 5 80387639 81047638 6631 5 80387639
83280630
6588 5 80387639 81082921 6632 5 80387639
83281412
6589 5 80387639 81157909 6633 5 80387639
83400242
6590 5 80387639 81265937 6634 5 80387639
83405797
6591 5 80387639 81265937 6635 5 80387639
83437132
6592 5 80387639 81267485 6636 5 80387639
83522252
6593 5 80387639 81267499 6637 5 80387639
83560095
6594 5 80387639 81274512 6638 5 80387639
83560204
6595 5 80387639 81763618 6639 5 80387639
83572400
6596 5 80387639 81797217 6640 5 80387639
83607661
6597 5 80387639 81800186 6641 5 80387639
83745342
6598 5 80387639 81806213 6642 5 80387639
83861275
6599 5 80387639 81854583 6643 5 80387639
83861633
6600 5 80387639 81859374 6644 5 80387639
83865653
6601 5 80387639 81861368 6645 5 80387639
83865914
6602 5 80387639 81863686 6646 5 80387639
83865920
6603 5 80387639 81916850 6647 5 80387639
83868010
6604 5 80387639 81954891 6648 5 80387639
84019752
6605 5 80387639 81985250 6649 5 80387639
84065912
6606 5 80387639 82083752 6650 5 80387639
84086632
6607 5 80387639 82101253 6651 5 80387639
84089603
6608 5 80387639 82143124 6652 5 80387639
84104814
6609 5 80387639 82236318 6653 5 80387639
84105175
6610 5 80387639 82325587 . 6654 5 80387639
84251635
185
CA 0 2 9 3 95 8 0 2 0 1 6 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chn Boundaryl Boundary2 Segment Chn Boundaryl Boundary2
6655 5 80387639 84252180 6699 5 80388596 81274512
6656 5 80387639 84253030 6700 5 80388596 81763618
6657 5 80387639 84254208 6701 5 80388596 81797217
6658 5 80387639 84314930 6702 5 80388596 81800186
6659 5 80387639 84340523 6703 5 80388596 81806213
6660 5 80387639 84516340 6704 5 80388596 81854583
6661 5 80387639 84706916 6705 5 80388596 81859374
6662 5 80387639 84799488 6706 5 80388596 81861268
6663 5 80387639 84801081 6707 5 80388596 81863686
6664 5 80387639 84824103 6708 5 80388596 81916850
6665 5 80387639 84824203 6709 5 80388596 81954891
6666 5 80387639 84824816 6710 5 80388596 81985250
6667 5 80387639 84825422 6711 5 80388596 82083752
6668 5 80387639 84825763 6712 5 00388596 82101253
6669 5 80387639 84825942 6713 5 80388596 82143124
6670 5 80387639 64843411 6714 5 80388596 82236318
6671 5 80387639 84936441 6715 5 80388596 82325587
6672 5 80387639 84936493 6716 5 80388596 82427210
6672 5 80387639 84943705 6717 5 80388596 82431893
6674 5 80387639 169454950 6718 5 80388596 82446714
6675 5 80387639 181522829 6719 5 80388596 82446794
6676 5 80387639 204759879 6720 5 80388596 82551111
6677 5 80387639 209874191 6721 5 80388596 82552090
6678 5 80368596 80389787 6722 5 80388596 82555641
6679 5 80388596 80411639 6723 5 80388596 82555670
6680 5 80388596 80446855 6724 5 80388596 82556511
6681 5 80388596 80492790 6725 5 80388596 82559047
6682 5 80388596 80670554 6726 5 80388596 82561535
6683 5 80388596 80674679 6727 5 80388596 82610100
6684 5 80388596 80720509 6728 5 80388596 82676822
6685 5 80388596 80800856 6729 5 80388596 82676901
6686 5 80388596 80804587 6730 5 80388596 82883691
6687 5 80388596 80807409 6731 5 80388596 82954942
6688 5 80388596 80835734 6732 5 80388596 82971688
6689 5 80388596 80971764 6733 5 80388596 83023965
6690 5 80388596 80972258 6734 5 80388596 83094205
6691 5 80388596 80974450 6735 5 80388596 83146355
6692 5 803811596 81047638 6736 5 80388596 83280630
6693 5 80388596 81082921 6737 5 80388596 83281412
6694 5 80388596 81157909 6738 5 80388596 83400242
6695 5 80388596 81265937 6739 5 80388596 83405797
6696 5 80388596 81265937 6740 5 80388596 83437132
6697 5 80388596 81267485 6741 5 80388596 83522252
6698 5 80388596 81267499 6742 5 80388596 83560095
186
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chonnosonnal
Segment Om Boundmy 1 Boundary2 Segment Chr, Boundaryl
Boundary2
6743 5 80388596 83560204 6787 5 80411337
80674679
6744 5 80388596 83572400 6788 5 80411337
80720509
6745 5 80388596 83607661 6789 5 80411337
80800856
6746 5 80388596 83745342 6790 5 80411337
80804587
6747 5 80388596 83861275 6791 5 80411337
80807409
6748 5 80388596 83661633 6792 5 80411337
80835734
6749 5 80388996 83865653 6793 5 80411337
80971764
6750 5 80388596 83865914 6794 5 80411337
80972258
6751 5 80388596 83065920 6799 5 80411337
80974450
6752 5 80388596 83868010 6796 = 5 80411337
81047638
6753 5 80388596 84019752 6797 5 80411337
81082921
6754 5 80388596 84065912 6798 5 80411337
81157909
6755 5 80388596 84086632 6799 5 80411337
81265937
6756 5 80388596 84089603 6800 5 80411337
01265937
6757 5 80388596 84104814 6801 5 80411337
81267485
6758 5 80388596 84105175 6802 5 80411337
81267499
6759 5 80388596 84251635 6803 5 80411337
81274512
6760 5 80388596 84252180 6804 5 80411337
81763618
6761 5 80388596 84253030 6805 5 80411337
81797217
6762 5 80388596 84254208 6806 5 00411337
81800186
6763 5 80388596 84314930 6807 5 80411337
81806213
6764 5 80388596 84340523 6808 5 80411337
81854583
6765 5 80388596 64516340 6809 5 80411337
81859374
6766 5 80388596 84706916 6810 5 00411337
81861368
6767 5 80388596 84799488 6811 5 80411337
81863686
6768 5 80388596 84801081 6812 5 80411337
81916850
6769 5 80388596 84824103 6813 5 80411337
81954891
6770 5 80388596 84824203 6814 5 80411337
81985250
6771 5 80388596 84824816 6815 5 80411337
82083752
6772 5 80388596 84825422 6816 5 80411337
82101253
6773 5 80388596 84825763 6817 5 80411337
82143124
6774 5 80388596 84825942 6818 5 80411337
82236318
6775 5 80388596 84843411 6819 5 80411337
82325587
6776 5 80388596 84936441 6820 5 80411337
82427210
6777 5 80388596 84936493 6821 5 80411337
82431853
6778 5 80388596 84943705 6822 5 80411337
82446714
6779 5 80388596 165494950 6823 5 80411337
82446794
6780 5 80388596 181522829 6824 5 80411337
82551111
6781 5 80388596 204759879 6625 5 80411337
82552090
6782 5 80388596 209874191 6626 5 80411337
82555641
6783 9 80411337 80411639 6827 5 80411337
82555670
6784 5 80411337 80446855 6828 5 80411337
82556511
6785 5 80411337 80492790 6829 5 80411337
82559047
6786 5 80411337 80670554 6830 5 80411337
82561535
187
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment ChE Boundary 1 Boundary2 Segment Chr. Boundary 1
13ounthry2
6831 5 80411337 82610100 6875 5 80411337
84824816
6832 5 80411337 82676822 6876 5 80411337
84825422
6833 5 80411337 82676901 6877 5 80411337
84825763
6834 5 80411337 82883691 6878 5 80411337
84825942
6835 5 80411337 82954942 6879 5 80411337
84843411
6836 5 80411337 82971688 6880 5 80411337
84936441
.6837 5 80411337 83023965 6881 5 80411337
04936493
6838 5 80411337 _ 83094205 6882 5 .. 80411337 ..
84943705
6839 5 80411337 83146355 6883 5 80411337
169454950
6840 5 80411337 83280630 6884 5 80411137
181522829
6841 5 80411337 83281412 6885 5 80411337
204759879
6842 5 80411337 83400242 6886 5 80411337
209874191
6843 5. 80411337 83105797 6887 5 80446281
80446855
6844 5 80411337 83437132 6888 5 80446281
80492790
6845 5 80411337 83522252 6889 5 80446281
80670554
6846 5 80411337 83560095 6890 5 80446281
80674679
6847 5 80411337 83560204 6891 5 80446281
80720509
6848 5 80411337 83572400 6892 5 80446281
80800856
. 6849 5 80411337 83607661 6893 5 80446281
80804587
6850 5 80411337 83745342 6894 5 80446281
80807409
6851 5 80411337 83861275 6895 5 80446281
80835734
6852 5 80411337 83861633 6896 5 80446281
80971764
6853 5 80411337 83865653 6897 5 80446281
80972258
6854 5 80411337 83865914 6898 5 80446281
80974450
6855 5 80411337 83865920 6899 5 80446281
81047638 .
6856 5 80411337 83868010 6900 5 80416281
81082921
6857 5 80411337 84019752 6901 5 80446281
81157909
6858 5 80411337 84065912 6902 5 80446281
81265937
6859 5 80411337 84086632 6903 5 80446281
81265937
6860 5 80411337 84089603 6904 5 80146281
81267485
6861 5 80411337 84104814 6905 5 80446281
81267499
6862 5 80411337 84105175 6906 5 80446281
81274512
6863 5 80411337 84251635 6907 5 80446281
81763618
6864 5 80411337 84252180 6908 5 80446281
81797217
6865 5 80411337 84253030 6909 5 80446281
81800186
6866 5 80411337 84254208 6910 5 80446281
81806213
6867 5 80411337 84314930 6911 5 80446281
81854583
6868 5 80411337 84340523 6912 5 80446281
81859374
6869 5 80411337 84516340 6913 5 80446281
81861368
6870 5 80411337 84706916 6914 5 80446281
81863686
6871 5 80411337 84799488 6915 5 80446281
81916850
6872 5 80411337 84801081 6916 5 80446281
81954891
6873 5 80411337 84824103 6917 5 80446281
81985250
6874 5 80411337 84824203 6918 5 80446281
82083752
188
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosome] Chromosomal
Segment Chr. Boundary1 Boundary2 Segment Chr. 64oun1ary1 Boundary2
6919 5 80446281 82101253 6963 5 80446281
84089603
6920 5 80446281 82143124 6964 5 80446281
84104814
6921 5 80446281 82236318 6965 5 80446281
84105175
6922 5 80446281 82325587 6966 5 80446281
84251635
6923 5 80446281 82427210 6967 5 80446281
84252180
6924 5 80446281 82431853 6968 5 80446281
84253030 .
6925 5 80446281 82446714 6969 5 80446281
84254208
6926 5 80446281 82446794 6970 5 80446281
84314930
6927 5 80446281 82551111 6971 5 80446281
84340523
6928 5 80446281 82552090 6972 5 80446281
84516340
6929 5 80446281 82555641 6973 5 80446281
84706916
6930 5 80446281 82555670 6974 5 80446281
84799488
6931 5 80446281 . 82556511 6975 . 5 80446281 84801081
6932 5 80446281 82559047 6976 5 80446281
84024103
6933 5 80446281 82561535 6977 5 80446281
84824203
6934 5 80446281 82610100 6978 5 80446281
84824816 '
6935 5 80446281 82676822 6979 5 80446281
84825422
6936 5 80446281 82676901 6980 5 80446281
84825763
6937 5 80446281 82883691 6981 5 80446281
84825942
6938 5 80446281 82954942 6982 5 .80416281
84843411
6939 ' 5 80446281 82971688 6983 5 80446281 84936441
6940 5 80446281 83023965 6984 5 80446281
84936493
6941 5 80446281 83094205 6985 5 80446281
84943705
6942 5 80446281 83146355 6986 5 80446281
169454950
6943 5 80446281 83280630 6987 5 80446281
181522829
6944 5 80446281 83281412 6988 5 80446281
204759879
6945 5 80446281 83400242 6989 5 80446281
209874191
6946 5 80446281 83405797 6990 5 80491807
60492790
6947 5 80446281 83437132 6991 5 80491807
80670554
6948 5 80446281 83522252 6992 5 80491887
80674679
6949 5 80446281 83560095 6993 5 80491807
80720509
6950 5 80446281 83560204 6994 5 80491807
80800856
6951 5 80446281 83572400 6995 5 80491807
80804587
6952 5 80446281 83607661 . 6996 5 80491807
80807409
6953 5 80446281 83745342 6997 5 80491807
80835734
6954 5 80446281 83861275 6998 5 80491807
80971764
6955 5 80446281 83861633 6999 5 80491807
80972258
6956 5 80446281 01865653 7000 5 80491807
80974450
6957 5 80416281 83865914 7001 5 80491807
81047638
6958 5 80446281 83865920 7002 5 80491807
81082921
6959 5 80446281 83868010 7003 5 80491807
81157909
6960 5 80446281 84019752 7004 5 80491807
81265937
6961 5 80446281 84065912 7005 5 80491807
81265937
6962 5 80446281 84086632 7006 5 80491807
81267485
189
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary2 Segment Chr. Boundaryl
Boundary2
7007 5 80491807 81267499 7051 5 80491807 83560095
7008 5 80491807 81274512 7052 5 80491807 83560204
7009 5 80491807 81763618 7053 5 80491807 83572400
7010 5 80491807 81797217 7054 5 80491807 83607661
7011 5 80491807 81800186 7055 5 80491807 83745342
7012 5 80491807 81/306213 7056 5 80491807 83861275
7013 5 80491807 81854583 7057 5 80491807 83861633
7014 5 80491807 81859371 7058 5 80491807 83865653
7015 5 80491807 81861368 7059 5 80491807 83865914
7016 5 80491807 61863686 7060 5 80491807 83865920
7017 5 80491807 81916850 7061 5 80491807 83868010
7018 5 80491807 81954891 7062 5 80491807 84019752
7019 5 80491807 81985250 7063 5 80491807 84065912
7020 5 80491807 82083752 7064 5 80491807 84086632
7021 5 80491807 82101253 7065 5 80491807 84089603
7022 5 80491807 82143124 7066 5 80491807 84104814
7023 5 80491807 82236310 7067 5 80491807 84105175
7024 5 80491807 82325587 7068 5 80491807 84251635
7025 5 80491807 82427210 7069 5 80491807 84252180
7026 5 80491807 82431853 7070 5 80491807 84253030
7027 5 80491807 82446714 7071 5 80491807 84254208
7028 5 80491807 82446794 7072 5 80491007 84314930
7029 5 80491807 82551111 7073 5 80491807 84340523
7030 5 80491807 82552090 7074 5 80491807 84516340
7031 5 80491807 82555641 7075 5 80491807 84706916
7032 5 80491807 82555670 7076 5 80491807 84799488
7033 5 80491807 82556511 7077 5 80491807 84801081
7034 5 80491807 82559047 7078 5 80491807 84824103
7035 5 80491807 82561535 7079 5 80491807 84824203
7036 5 80491807 82610100 7080 5 80491807 84824816
7037 5 80491807 82676822 7081 5 80491807 84825422
7038 5 80491807 82676901 7082 5 80491807 84825763
7039 5 80491807 82883691 7083 5 80491807 84825942
7040 5 80491807 82954942 7084 5 80491807 84843411
7041 5 80491807 82971688 7085 5 80491807 84936441
7042 5 80491807 83023965 7086 5 80491807 84936493
7043 5 80491/107 83094205 7087 5 80491807 84943705
7044 5 80491807 83146355 7088 5 80491807 169454950
7045 5 80491807 83280630 7089 5 80491807 181522829
7046 5 80491807 83281412 7090 5 80491807 204759879
7047 5 80491807 83400242 7091 5 80491807 209874191
7048 5 80491807 83405797 7092 5 80669160 80670554
7049 5 80491807 83437132 7093 5 80669160 80674679
7050 5 80491807 83522252 7094 5 80669160 80720509
190
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chrmnommnal Chromosomal
Segment Clm Boundary1 Boundary2 Segment Om Boundary!
Boundary2
7095 5 80669160 80800056 7139 5 80669160
82676901
7096 5 80669160 80804587 7140 5 80669160
82883691 --
7097 5 80669160 80807409 7141 5 80669160
82954942
7091 5 80669160 80835734 7142 5 80669160
82971688
7099 5 80669160 80971764 7143 5 80669160
83023965
7100 5 80669160 80972258 7144 5 80669160
83094205
7101 5 80669160 80974150 7145 5 80669160
83146355
7102 5 80669160 81047638 7146 5 80669160
83280630
7103 5 80669160 81082921 7147 5 80669160
83281412
7104 5 80669160 81157909 7148 5 80669160
83400242
7105 5 80669160 81265937 7149 5 80669160
83405797
7106 5 80669160 81265937 7150 5 80669160
83437132
7107 5 80669160 81267485 7151 5 80669160
83522252
7108 5 80669160 81267499 7152 5 80669160
83560095
7109 5 80669160 11274512 7153 5 80669160
83560204
7110 5 80669160 81763618 7154 5 80669160
83572400
7111 5 80669160 81797217 7155 5 80669160
83607661
7112 5 80669160 81800186 7156 5 80669160
83745342
7113 5 80669160 81806213 7157 5 80669160
83861275
7114 5 80669160 81854583 7158 5 80669160
83861633
7115 5 80669160 81859374 7159 5 80669160
83865653
7116 5 80669160 81861368 7160 5 80669160
83865914
7117 5 80669160 81863686 7161 5 80669160
83865920
7118 5 80669160 81916850 7162 5 80669160
13868010
7119 5 80669160 81954891 7163 5 80669160
84019752
7120 5 80669160 81985250 7164 5 80669160
84065912
7121 5 80669160 82083752 7165 5 80669160
84086632
7122 5 80669160 82101253 7166 5 80669160
84089603
7123 5 80669160 82143124 7167 5 80669160
84104814
7124 5 80669160 82236318 7168 5 80669160
84105175
7125 5 80669160 82325587 7169 5 80669160
84251635
7126 5 80669160 82427210 7170 5 80669160
84252180
7127 5 80669160 82431853 7171 5 80669160
84251030
7128 5 80669160 82446714 7172 5 80669160
84254208
7129 5 80669160 82446794 7173 5 80669160
84314930
7130 5 80669160 82551111 7174 5 80669160
84340523
7131 5 80669160 82552090 7175 5 80669160
84516340
7132 5 80669160 82555641 7176 5 80669160
84706916
7133 5 80669160 82555670 7177 5 80669160
84799488
7134 5 80669160 82556511 7178 5 80669160
84801081
7135 5 80669160 82559047 7179 5 80669160
84824103
7136 5 80669160 82561535 7180 5 80669160
84824203
7137 5 80669160 82610100 7181 5 80669160
84824816
7138 5 80669160 82676822 7182 5 80669160
84825422
191 ,
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment am Boundani1 Boundary2 Segment Cite. Boundary1 Boundary2
7183 5 80669160 84825763 7227 5 80715081 82446714
7184 5 80669160 84825942 7228 5 80715081 82446794
7185 5 80669160 84843411 7229 5 80715081 82551111
7186 5 80669160 84936441 7230 5 80715081 82552090
7117 5 80669160 84936493 7231 5 80715081 82555641
7188 5 80669160 84943705 7232 5 80715081 82555670
7189 5 80669160 169454950 7233 5 80715081 82556511
7190 5 80669160 181522829 7234 5 80715081 82559047
7191 5 80669160 204759879 7235 5 80715081 82561535
7192 5 80669160 209874191 7236 5 80715081 82610100
7193 5 80715081 80720509 7237 5 80715081 82676822
7194 5 80715081 80800856 7230 5 80715081 82676901
7195 5 80715081 80804587 7239 5 80715081 82883691
7196 5 80715081 80807409 7240 5 80715081 82954942
7197 5 80715081 80835734 7241 5 80715081 82971688
7198 5 80715081 80971764 7242 5 80715081 83023965
7199 5 80715081 80972258 7243 5 80715081 83094205
7200 5 80715081 80974450 7244 5 80715081 83146355
7201 5 80715081 81047638 7245 5 80715081 83280630
7202 5 80715081 81082921 7246 5 80715081 83281412
7203 5 80715081 81157909 7247 5 80715081 83400242
7204 5 80715081 81265937 7248 5 80715081 83405797
7205 5 80715081 81265937 7249 5 80715081 83437132
7206 5 80715081 81267485 7250 5 80715081 83522252
7207 5 80715081 81267499 7251 5 80715081 83560095
7208 5 80715081 81274512 7252 5 80715081 83560204
7209 5 80715081 81763618 7253 5 80715081 83572400
7210 5 80715081 81797217 7254 5 80715081 83607661
7211 5 80715081 81800186 7255 5 80715081 83745342
7212 5 80715081 81806213 7256 5 80715081 83861275
7213 5 80715081 81854583 7257 5 80715081 83861633
7214 5 80715081 81859374 7258 5 80715081 83865653
7215 5 80715081 81861368 7259 5 80715081 83865914
7216 5 80715081 81863686 7260 5 80715081 83865920
7217 5 0715081 81916850 7261 5 80715081 83868010
7218 5 80715081 81954891 7262 5 80715081 84019752
7219 5 80715081 81985250 7263 5 80715081 84065912
7220 5 80715081 82083752 7264 5 80715081 84086632
7221 5 80715081 82101253 7265 5 80715081 84089603
7222 5 80715081 82143124 7266 5 80715001 84104814
7223 5 80715081 82236318 7267 5 80715081 84105175
7224 5 80715081 82325587 7268 5 80715081 84251635
7225 5 80715081 82427210 7269 5 80715081 84252180
7226 5 80715081 82431853 7270 5 80715081 84253030
192
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosound Chromosonull
Segment Cho. Boundary1 Boundary 2 Segment Cite.
Boundary1 Boun1ary2
7271 5 80715081 84254208 7315 5 80795990 81916850
. 7272 5 80715081 84314930 7316 5 80795990 81954891
7273 5 80715081 84340523 7317 5 80795990 81985250
7274 5 80715681 84516340 7318 5 80795990 82083752
7275 5 80715081 84706916 7319 5 80795990 82101253
7276 5 80715081 84799488 7320 5 80795990 82143124
7277 5 80715081 84801081 7321 5 80795990 82236318
7278 5 80715081 84824103 7322 5 80795990 82325587
7279 5 80715081 84824203 7321 5 80795990 82427210
7280 5 80715081 84824816 7324 5 80795990 82431853
7281 5 80715081 84825422 7325 5 80795990 . 82446714
7282 5 80715081 84825763 7326 5 80795990 82446794
7283 5 80715081 84825942 7327 5 80795990 82551111
7284 5 80715081 84843411 7328 5 80795990 82552090
7285 5 80715081 84936441 7329 5 80795990 82555641
7286 5 80715081 84936493 7330 5 80795990 82559670
7287 5 80715081 84943705 7331 5 80799990 82556511
7288 5 80715081 169454950 7332 5 80795990 82559047
7289 5 80715081 181522829 7333 5 80795990 82561535
7290 5 80715081 204759879 7334 5 80795990 82610100
7291 5 80715081 209874191 7335 5 80795990 82676822
7292 5 80795990 80800856 7336 5 80795990 82676901
7293 5 80795990 80804587 7337 5 80795990 82883691
7294 5 80795990 80807409 7338 5 80795990 82954942
7295 5 80795990 80835734 7339 5 80795990 82971688
7296 5 80795990 80971764 7340 5 80795990 83023965
7297 5 80795990 80972258 7341 5 80795990 83094205
7298 5 80795990 80974450 7342 5 80795990 83146355
7299 5 80795990 81047638 7343 5 80795990 83280630
7300 5 80795990 81082921 7344 5 80795990 83281412
7301 5 80795990 81157909 7345 5 80799990 83400242
7302 5 80795990 81265937 7346 5 80795990 83405797
7303 5 00795990 81265937 7347 5 80795990 83437132
7304 5 80795990 81267485 7348 5 80795990 83522252
7305 5 80795990 81267499 7349 5 80795990 83560095
7306 5 80795990 81274512 7350 5 80795990 83560204
7307 5 80795990 81763618 7351 5 80795990 83572400
7308 5 80795990 81797217 7352 5 80795990 83607661
7309 5 80795990 81800186 7353 5 80795990 83745342
7310 5 80795990 81806213 7354 5 80795990 83861275
7311 5 80795990 81854583 7355 5 80795990 83861633
7312 5 10795990 81859374 7356 5 80795990 83865653
7313 5 80795990 81861368 7357 5 80795990 83865914
7314 5 80795990 81863666 7358 5 80795990 83865920
193
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundmyl Boundary 2 Segment Chn Boundary 1
Boundary2
7359 5 80795990 83868010 7403 5 80803727
81274512
7360 5 80795990 84019752 7404 5 80803727
81763618
7361 5 80795990 84065912 7405 5 80803727
81797217
7362 5 80795990 84086632 7406 5 80803727
81800186
7363 5 80795990 84089603 7407 5 80803727
81806213
7364 5 80795990 84104814 7408 5 80803727
81854583
7365 5 80795990 84105175 7409 5 80803727
81859374
7366 5 80795990 84251635 7410 5 80803727
81861368 .
7367 5 80795990 84252180 7411 5 80803727
81861686
=
7368 5 80795990 84253030 7412 5 80803727
81916050
7369 5 80795990 84254208 7413 5 80803727
81954891
7370 5 80795990 84314930 7414 5 80803727
81985250
7371 5 80795990 84340523 7415 5 80803727
82083752
7372 5 80795990 84516340 7416 5 80803727
82101253
7373 5 80795990 84706916 7417 5 80803727
12143124
7374 5 80795990 84799488 7418 5 80/103727
82236318
7375 5 80795990 114801081 7419 5 80803727
82325587
7376 5 80795990 84824103 7420 5 80803727
82427210
7377 5 80795990 84824203 7421 9 80803727
82431853
7378 5 80795990 84824816 7422 5 80803727
82446714
7379 5 80795990 84825422 7423 5 80803727
82446794
7380 5 80795990 84825763 7424 5 80803727
82551111
7381 5 80795990 84825942 7425 5 80803727
82552090
7382 5 80795990 84843411 7426 5 80803727
82555641
7383 5 80795990 84936441 7427 5 80803727
82555670
7184 5 80795990 84936493 7428 5 80803727
82556511
7385 5 80795990 84943705 7429 5 80803727
82559047
7386 5 80795990 169454950 7430 5 80803727
82561535
7387 5 80795990 181522829 7431 5 80803727
82610100
7388 5 80795990 204759879 7432 5 80803727
82676822
7389 5 80795990 209874191 7433 5 80803727
82676901
7390 5 80803727 80804587 7434 5 80803727
82883691
7391 5 80803727 80807409 7435 5 80803727
82954942
7392 5 80803727 80835734 7436 5 80803727
82971688
7393 5 80803727 80971764 7437 5 80803727
83023965
7394 5 80803727 80972258 7438 5 80803727
83094205
7395 5 80803727 80974450 7439 5 80803727
83146355
7396 5 80803727 81047638 7440 5 80803727
83280630
7397 5 80803727 81082921 7441 5 80803727
83281412
7398 5 80803727 81157909 7442 5 80803727
83400242
7399 5 80803727 81265937 7443 5 80803727
83405797
7400 5 80803727 81265937 7444 5 80803727
83437132
7401 5 80803727 81267485 7445 5 80803727
83522252
7402 5 80803727 81267499 7446 5 80803727
83560095
194
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Ciwornosontal
Segment Chr. Boundary 1 Boundary2 Segment Cho.
Boundary1 Boundary2
7447 5 80803727 83560204 7491 5 80804587
81047638
7448 5 80803727 83572400 7492 5 80804587
81082921
7449 5 80803727 83607661 7493 5 80804587
81157909
7450 5 80803727 83745342 7494 5 80804587
81265937
7451 5 80803727 83861275 7495 5 80804587
81265937
7452 5 80803727 83861633 7496 5 80804587
81267485
7453 5 80803727 83865653 7497 5 80804587
81267499
7454 5 80803727 83865914 7498 5 80804587
81274512
7455 5 80803727 83865920 7499 5 80804587
81763618
7456 5 80803727 81868010 7500 5 80804587
81797217
7457 5 80803727 84019752 7501 5 80804587
81800186
7458 5 80803727 84065912 7502 5 80804587
81806213
7459 5 80801727 84086632 7503 5 80804587
81854583
7460 5 80803727 84089603 7504 5 80804587
81859374
7441 5 80803727 84104814 7505 5 80804587
81861368
7462 5 80803727 84105175 7506 5 80804587
81863686
7463 5 80803727 84251635 7507 5 80804587
81916850
7464 5 80803727 84252180 7508 5 80804587
81954891
7465 5 80803727 84253030 7509 5 80804587
81985250
7466 5 80803727 84254208 7510 5 80804587
82083752
7467 5 80803727 84314930 7511 5 80804587
82101253
7468 5 80883727 84340523 7512 5 80804587
82143124
7469 5 80803727 84516340 7513 5 80804587
82236318
7470 5 80803727 84706916 7514 5 80804587
82325587
7471 5 80803727 84799486 7515 5 80804587
82427210
7472 5 88803727 84801081 7516 5 80804587
82431853
7473 5 80803727 84824103 7517 5 80804587
82446714
7474 5 80803727 84824203 7518 5 80804587
82446794
7475 5 80803727 84824816 7519 5 80804587
82551111
7476 5 80803727 84825422 7520 5 80804587 '
82552090
7477 5 80803727 84825763 7521 5 80804587
82555641
7478 5 80803727 84825942 7522 5 80804587
82555670
7479 5 80803727 84843411 7523 5 80804587
82556511
7480 5 80803727 84936441 7524 5 80804587
82559047
7481 5 80803727 84936493 7525 5 80804587
82561535
7482 5 80803727 84943705 7526 5 80804587
82610100
7483 5 80803727 169454950 7527 5 80804507
82676822
7484 5 80803727 181522829 7528 5 80804587
82676901
7485 5 80803727 204759879 7529 5 80804587
82883691
7486 5 80803727 209874191 7530 5 80804587 82954942
7487 5 80804587 80835734 7531 5 80804587
82971688
7488 5 80804587 80971764 7532 5 80804587
83023965
7489 5 80804587 80972258 7533 5 80804587
83094205
7490 5 80804587 80974450 7534 5 80804587
83146355
195
CA 02 93 9580 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
'fable 1 (contd.)
Chromosomal Chromosomal
Segment Chr, Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
7535 5 80804587 83280630 7579 5 80804587 181522829
7536 5 80804587 83281412 7580 5 80804587 204759879
7537 5 80804587 83400242 7581 5 80804587 209874191
7538 5 80804587 83405797 7582 5 80828457 80835734
7539 5 80804587 83437132 7583 5 80828457 80971764
7540 5 80804587 83522252 7584 5 80828457 80972258
7541 5 80804587 83560095 7585 5 80828457 80974450
7542 5 80804587 83560204 7586 5 80828457 81047638
7543 5 80804587 83572400 7587 5 80828457 81082921
7544 5 80804587 83607661 7588 5 80828457 81157909
7545 5 80804587 83745342 7589 5 80828457 81265937
7546 5 80804587 83861275 7590 5 80828457 81265937
7547 5 80804587 83861633 7591 5 80828457 81267485
7548 5 80804587 83865653 7592 5 80828457 81267499
7549 5 80804587 83865914 7593 5 80828457 81274512
7550 5 80804587 83865920 7594 5 80828457 81763618
7551 5 80804587 83868010 7595 5 80828457 81797217
7552 5 80804587 84019752 7596 5 80828457 81800186
7553 5 80804587 84065912 7597 5 80828457 81806213
7554 5 80804587 84086632 7598 5 801128457 81854583
7555 5 80804587 84089603 7599 5 80828457 81859374
7556 5 80804587 84104814 7600 5 80828457 81861368
7557 5 80804587 84105175 7601 5 80828457 81863686
7558 5 80804587 84251635 7602 5 80828457 81916850
7559 5 80804587 84252180 7603 5 80828457 81954891
7560 5 80804587 84253030 7604 5 80828457 81985250
7561 5 80804587 84254208 7605 5 80828457 82083752
7562 5 80804587 84314930 7606 5 80828457 82101253
7563 5 80804587 84340523 76.07 5 80828457 82143124
7564 5 80804587 84516340 7608 5 80828457 82236318
7565 5 80804587 84706916 7609 5 80828457 82325587
7566 5 80804587 84799488 7610 5 80828457 82427210
7567 5 80804587 84801081 7611 5 80828457 82431853
7568 5 80804587 84824103 7612 5 80828457 82446714
7569 5 80804567 84824203 7613 5 80828457 82446794
7570 5 80804587 84824816 7614 5 80828457 82551111
7571 5 80804587 84825422 7615 5 80828457 82552090
7572 5 80804587 84825763 7616 5 80828457 82555641
7573 5 80804587 84825942 7617 5 80828457 82555670
7574 5 80804587 84843411 7618 5 80828457 82556511
7575 5 80804587 84936441 7619 5 80828457 82559047
7576 5 80804587 84936493 7620 5 80828457 82561535
7577 5 80804587 84943705 7621 5 80828457 82610100
7578 5 80804587 169454950 7622 5 80828457 82676822
196
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chnmmosmnd
Segment Chr. 13oundary1 Boundao/2 Segment CM. Boundary1
Boundary2
7623 5 80828457 82676901 7667 5 80828457
84825763
7624 5 80828457 82883691 7668 5 '80828457
84825942
7625 5 80828457 82954942 7669 5 80828457
84843411
7626 5 80828457 82971688 7670 5 80828457
84936441
7627 5 80828457 83023965 7671 5 80828457
84936493
7628 5 80828457 83094205 7672 5 80828457
84943705
7629 5 80828457 83146355 7673 5 80828457
169454950
7630 5 80828457 83280630 7674 5 80828457
181522829
7631 5 80828457 83281412 7675 5 80828457
204759879
7632 5 80828457 83400242 7676 5 , 80828457
209874191
7633 5 80828457 83405797 7677 5 80828945
80835734
7634 5 80828457 83437132 7678 5 80828945
80971764
7635 5 80828457 83522252 7679 5 80828945
80972258
7636 5 80828457 83560095 7680 5 80828945
80974450
7637 5 80828457 83560204 7681 5 80828945
81047638
7638 5 80828457 83572400 7682 5 80828945
81082921
7639 5 80828457 83607661 7683 5 80828945
81157909
7640 5 80828457 83745342 7684 5 80828945
81265937
7641 5 80828457 83861275 7685 5 80828945
81265937
7642 5 80828457 83861633 7686 5 80828945
81267485
7643 5 80828457 83865653 7687 5 80828945
81267499
7644 5 80828457 83865914 7688 5 80828945
81274512
7645 5 80828457 83865920 7689 5 80828945
81763618
7646 5 80828457 8389010 7690 5 80828945
81797217
7647 5 80828457 84019752 7691 5 80828945
01800186
7648 5 80828457 84065912 . 7692 5 80828945
81806213
7649 5 80828457 84086632 7693 5 80828945
81854583
7650 5 80828457 84089603 7694 5 80828945
81859374
7651 5 80828457 84104814 7695 5 80828945
81861368
7652 5 80828457 84105175 7696 5 80828945
81863686
7653 5 80828457 84251635 7697 5 80828945
81916850
7654 5 80828457 81252180 7698 5 80828945
81954891
7655 5 80828457 84253030 7699 5 80828945
81985250
7656 5 80828457 84254208 7700 5 80828945
82083752
7657 5 80828457 84314930 7701 5 80828945
82101253
7658 5 80828457 84340523 7702 5 80828945
82143124
7659 5 80828457 84516340 7703 5 80828945
82236318
7660 5 80828457 84706916 7704 5 80828945
82325587
7661 5 80828457 84799488 7705 5 80828945
82427210
7662 5 80828457 84801081 7706 5 00828945
82431853
7663 5 80828457 84824103 7707 5 80828945
82446714
7664 5 80828457 84824203 7708 5 80828945
82446794
7665 5 80828457 84824816 7709 5 80828945
82551111
7666 . 5 80828457 84825422 7710 . 5 80828945
82552090
197 -
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosanud Chrommanal
Segment Chr. Boundary 1 Boundary2 Segment Cho. Boundary1
Boundary2
7711 5 80828945 82555641 7755 5 80828945
84706916
7712 5 80828945 82555670 7756 5 80828945
84799488
7713 5 80828945 82556511 7757 5 80828945
84801081
7714 5 80828945 82559047 7758 5 80828945
84824103
7715 5 80828945 82561535 7759 5 80828945
84824203
7716 5 80828945 82610100 7760 5 80828945
84824816
7717 5 80820945 82676822 7761 5 80828945
84825422
7718 5 80828945 82676901 7762 5 80828945
84825763
7719 5 80828945 82883691 7763 5 80828945
84825942
7720 5 80828945 82954942 7764 5 80828945
84843411
7721 5 80828945 82971688 7765 5 80828945
84936441
7722 5 80828945 83023965 7766 5 80828945
84936493
7723 5 80828945 83094205 7767 5 80828945
84943705
7724 5 80828945 83146355 7768 5 80828945
169454950
7725 5 80828945 83280630 7769 5 80828945
181522829
7726 5 80828945 83281412 7770 5 80828945
204759879
7727 5 80828945 83400242 7771 5 80828945
209874191
7728 5 80828945 83405797 7772 5 80969412
80971764
7729 5 80828945 83437132 7773 5 80969412
80972258
7730 5 80828945 83522252 7774 5 80969412
80974450
7731 5 80828945 83560095 7775 5 80969412
81047638
7732 5 80828945 83560204 7776 5 80969412
81012921
7733 5 80828945 83572400 7777 5 80969412
81157909
7734 5 80828945 83607661 7778 5 80969412
81265937
7735 5 80828945 83745342 7779 5 80969412
81265937
7736 5 80828945 83861275 7780 5 80969412
81267485
7737 5 80828945 83861633 7781 5 80969412
81267499
7738 5 80828945 83865653 7782 5 80969412
81274512
7739 5 80828943 83865914 7783 5 80969412
81763618
7740 5 80828945 83865920 7784 5 80969412
81797217
7741 5 80828945 83868010 7785 5 80969412
81800186
7742 5 80828945 84019752 7786 5 80969412
81806213
7743 5 80828945 84065912 7787 5 80969412
81854583
7744 5 80828945 84086632 7788 5 80969412
81859374
7745 5 80828945 84089603 7789 5 80969412
81861368
7746 5 80828945 84104814 , 7790 5 80969412
81863686
7747 5 80828945 84105175 7791 5 80969412
81916850
7748 5 80828945 84251635 7792 5 80969412
81954891
7749 5 80828945 84252180 7793 5 80969412
81985250
7750 5 80828945 84253030 7794 5 80969412
82083752
7751 5 80828945 81254208 7795 5 80969412
82101253
7752 5 80828945 84314930 7796 5 80969412
82143124
7753 5 80828945 84340523 7797 5 80969412
82236318
7754 5 80828945 84516340 7798 5 80969412
82325587
198
CA 0 2 9 3 95 8 0 2 0 1 6 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
,
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundaryl Boundary2 Segment Chr. Boundary1 Boundary2
7799 5 80969412 82427210 7843 5 80969412
84252180
7805 5 80969412 82431853 7844 5 80969412
84253030
7801 5 80969412 82446714 7845 5 80969412
84254208
7802 5 80969412 82446794 7846 5 80969412
84314930
7803 5 80969412 82551111 7847 5 80969412
84340523
7804 5 80969412 82552090 7848 5 80969412
84516340
7805 5 80969412 82955641 7849 5 80969412
84706916
7806 5 80969412 82555670 7850 5 80969412
84799488
7807 5 80969412 82556511 7851 5 80969412
84801081
7808 5 80969412 82559047 7852 5 80969412
84824103
7809 5 80969412 82561535 7853 5 8.0969412
84824203
7810 5 80969412 82610100 7854 5 80969412
84824816
7811 5 80969412 112676822 7855 5 80969412
84825422
7812 5 80969412 82676901 7856 5 80969412
84825763
7813 5 80969412 ' 82883691 7897 5 80969412
84825942
7814 5 80969412 82954942 7858 5 80969412
84843411
7815 5 80969412 82971688 7859 5 80969412
84936441
7816 5 80969412 83023965 7860 5 80969412
84936493
7817 5 80969412 83094205 7861 5 80969412
84943705
7818 5 80969412 83146355 7862 5 80969412
169454950
7819 5 80969412 83280630 7863 5 80969412
181522629
7820 5 80969412 83281412 7864 5 80969412
204759879
7821 5 80969412 83400242 7865 5 80969412
209874191
7822 5 80969412 63409797 7866 5 80970381
80974450
7823 5 80969412 83437132 7867 5 80970381
81047638
7824 5 80969412 83522252 7868 5 80970381
81082921
7825 5 80969412 83560095 7869 5 80970381
81157909
7826 5 80969412 83560204 7870 5 80970381
81265937
7827 5 80969412 83572400 7071 5 80970381
81265937
7828 5 80969412 83607661 7872 5 80970381
81267485
7829 5 80969412 83745342 7873 5 80970381
81267499
7830 5 80969412 83861275 7874 5 80970381
81274512
7831 5 80969412 83861633 7875 5 80970381
81763618
7832 5 80969412 83865653 7876 5 80970381
81797217
7833 5 80969412 83865914 7877 5 80970381
81800186
7834 5 80969412 83865920 7878 5 80970381
81806213
7835 5 80969412 83868010 7879 5 80970381
81854583
7836 5 80969412 84019752 7880 5 80970381
81859374
7837 5 80969412 84065912 7881 5 80970381
81861366
7838 5 80969412 84086632 7882 5 80970381
81863686
7839 5 80969412 84089603 7883 5 80970381
81916850
.7840 5 80969412 84104814 7884 5 80970381
81954891
7841 5 80969412 84105175 7885 5 80970381
81985250
7842 5 80969412 84251635 7886 5 80970381
82083752
199
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chaarnosonuil Chromosomal
Segment Chr. Boundary1 Bounthuy2 Segment Chc Boundary1
Boundary 2
7887 5 80970381 82101253 7931 5 80970381
84089603
7888 5 80970381 82143124 7932 5 80970381
84104814
7889 5 80970381 82236318 7933 5 80970381
84105175
7890 5 80970381 82325587 7934 5 80970381
84251635
7891 5 80970381 82427210 7935 5 80970381
84252180
7892 5 80970381 82431853 7936 5 80970381
84253030
7893 5 80970381 82446714 7937 5 80970381
84254208
7894 5 80970381 82446794 7938 5 80970381
84314930
7895 5 80970381 82551111 7939 5 80970381
84340523
7896 5 80970381 82552090 7940 5 80970381
84516340
7897 5 80970381 82555641 7941 5 80970381
84706916
7898 5 80970381 82555670 7942 5 80970381
84799488
7899 5 80970381 82556511 7943 5 80970381
84801081
7900 5 80970381 82559047 7944 5 80970381
84824103
7901 5 80970381 82561535 7945 5 80970381
84824203
7902 5 80970381 82610100 7946 5 80970381
84824816
7903 5 80970381 82676822 7947 5 80970381
84825422
7955 5 80970381 82676901 7948 5 80970381
84825763
7905 5 80970381 82883691 7949 5 80970381
84825942
7906 5 80970381 82954942 7950 5 80970381
84843411
7907 5 80970381 82971688 7951 5 80970381
84936441
7908 5 80970381 83023965 7952 5 80970381
84936493
7909 5 80970381 83094205 7953 5 80970381
84943705
7910 5 80970381 83146355 7954 5 80970381
169454950
7911 5 80970381 83280630 7955 5 80970381
181522829
7912 5 80970381 83281412 7956 5 80970381
204759879
7913 5 80970381 83400242 7957 5 80970381
209874191
7914 5 80970381 83405797 7958 5 80971764
81047638
7915 5 80970381 83437132 7959 5 80971764
81082921
7916 5 80970381 83522252 7960 5 80971764
81157909
7917 5 80970381 83560095 7961 5 80971764
81265937
7918 5 80970381 83560204 7962 5 80971764
81265937
7919 5 80970381 83572400 7963 5 80971764
81267485
7920 5 80970381 83607661 7964 5 80971764
81267499
7921 5 80970381 83745342 7965 5 80971764
81274512
7922 5 80970381 83861275 7966 5 80971764
81763618
7923 5 80970381 83861633 7967 5 80971764
81797217
7924 5 80970381 83865653 7968 5 80971764
81800186
7925 5 80970381 83865914 7969 5 80971764
81806213
7926 5 80970381 83865920 7970 5 80971764
81854583
7927 5 80970381 83868010 7971 5 80971764 _
81859374
7928 5 80970381 84019752 7972 5 80971764
81861368
7929 5 80970381 84065912 7973 5 80971764
81863686
7930 5 80970381 84086632 7974 5 80971764
81916850
200
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
'Fable 1 (contd.) ,
Chromnson3a1 Chromosome)
Segment CM. Boundary 1 Boundary2 Segment Chr. Boundary1
Boundary2
7975 5 80971764 81954891 8019 5 80971764
84019752
7976 5 80971764 81985250 8020 5 80971764
84065912
7977 5 80971764 82083752 8021 5 80971764
84086632
7978 5 80971764 82101253 8022 5 80971764
84089603
7979 5 80971764 82143124 - 8023 5 80971764
84104814 ,
7980 5 80971764 82236318 8024 5 80971764
84105175
7981 5 80971764 82325587 8025 5 80971764
84251635
7982 5 80971764 82427210 8026 5 80971764
84252180
7983 5 80971764 82431853 8027 5 80971764
84253030
7984 5 80971764 82446714 8028 5 80971764
84254208
7985 5 80971764 82446794 8029 5 80971764
84314930
7986 5 80971764 82551111 8030 5 80971764
84340523
7987 5 80971764 82552090 8031 5 80971764
84516340
7988 5 80971764 82555641 8032 5 80971764
84706916
7989 5 80971764 82555670 8033 5 80971764
84799488
7990 5 80971764 82556511 8034 5 80971764
84801081
7991 5 80971764 82559047 8035 5 80971764
84824103
7992 5 80971764 82561535 8036 5 80971764
84824203
7993 5 80971764 82610100 8037 5 80971764
84824816
7994 5 80971764 82676822 8038 5 80971764
84825422
7995 5 80971764 82676901 8039 5 80971764
84825763
7996 5 80971764 82883691 8040 5 80971764
84825942
7997 5 80971764 82954942 8041 5 80971764
84843411
7998 5 80971764 82971688 8042 5 80971764
84936441
7999 5 80971764 83023965 8043 5 80971764
84936493
8000 5 80971764 83094205 8044 5 80971764
84943705
8001 5 80971764 83146355 8045 5 80971764
169454950
8002 5 80971764 83280630 8046 5 80971764
181522829
8003 5 80971764 83281412 8047 5 80971764
204759879
8004 5 80971764 83400242 8048 5 80971764
209874191
8005 5 80971764 83405797 8049 5 81031951
81047638
8006 5 80971764 83437132 8050 5 81031951
81082921
8007 5 80971764 83522252 8051 5 81031951
81157909
8008 5 80971764 83560095 8052 5 81031951
81265937
8009 5 80971764 83560204 8053 5 81031951
81265937
8010 5 80971764 83572400 8054 5 81031951
81267485
8011 5 80971764 83607661 8055 5 81031951
81267499
8012 5 80971764 83745342 8056 5 81031951
81274512
8013 5 80971764 83861275 8057 5 81031951
81763618
8014 5 80971764 83861633 8058 5 81031951
81797217
8015 5 80971764 83865653 8059 5 81031951
81800186
8016 5 80971764 83865914 8060 5 81031951
81806213
8017 5 80971764 83865920 8061 5 81031951
81854583
8018 5 80971764 83868010 8062 5 81031951
81859374
201
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Clumnosouml
Segment Chn Boundary1 Boundary2 Segment Car. Boundary1 000ndmy2
8063 5 81031951 81861368 8107 5 81031951
83865914
8064 5 81031951 81863686 8108 5 81031951
03865920
8065 5 81031951 81916850 8109 5 81031951
83868010
8066 5 81031951 81954891 8110 5 81031951
84019752
8067 5 81031951 81985250 8111 5 81031951
84065912
8068 5 81031951 82083752 8112 5 81031951
84086632
8069 5 81031951 82101253 8113 5 81031951
84089603
8070 5 81031951 82143124 8114 5 81031951
84104814
8071 5 81031951 82236318 8115 5 81031951
84105175
8072 5 81031951 82325587 8116 5 81031951
84251635
8073 5 81031951 82427210 8117 5 81031951
84252180
8074 5 81031951 82431853 8118 5 81031951
84253030
8075 5 81031951 82446714 8119 5 81031951
84254208
8076 5 81031951 82446794 8120 5 81031951
84314930
8077 5 81031951 82551111 8121 5 81031951
84340523
8078 5 81031951 82552090 8122 5 81031951
84516340
8079 5 81031951 82555641 8123 5 81031951
84706916
8080 5 81031951 82555670 8124 5 81031951
84799488
8081 5 81031951 82556511 8125 5 81031951
84801081
8082 5 81031951 62559047 0126 5 81031951
84824103
0083 5 81031951 82561535 8127 5 81031951
84824203
8084 5 81031951 82610100 8128 5 81031951
84824816
8085 5 81031951 82676822 8129 5 81031951
84825422
8086 5 81031951 82676901 8130 5 81031951
84825763
8087 5 81031951 82883691 8131 5 81031951
84825942
8088 5 81031951 02954942 8132 5 81031951
844343411
8089 5 81031951 82971688 8133 5 81031951
84936441
8090 5 81031951 83023965 8134 5 81031951
84936493
8091 5 81031951 83094205 8135 5 81031951
84943705
8092 5 81031951 83146355 8136 5 81031951
169454950
8093 5 81031951 83280630 8137 5 81031951
181522829
8094 5 81031951 83281412 8138 5 81031951
204759879
8095 5 81031951 83400242 8139 5 81031951
209874191
8096 5 81031951 83405797 8140 5 81076870
81082921
8097 5 81031951 83437132 8141 5 81076870
81157909
8098 5 81031951 83522252 8142 5 81076870
81265937
8099 5 10031951 83560095 8143 5 81076870
81265937
8100 5 81031951 83560204 8144 5 81076870
81267485
8101 5 81031951 83572400 8145 5 81076870
81267499
8102 5 81031951 83607661 8146 5 81076870
81274512
8103 5 81031951 83745342 8147 5 81076870
81763618
8104 5 81031951 83861275 8148 5 81076870
81797217
8105 5 81031951 83861633 8149 5 81076870
81800186
8106 5 81031951 83865653 8150 5 81076870
81806213
202
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chrmnownmil
Segment Chr. Boundaryl Boundary2 Segment Ch/. Boundary 1
Boundmy2
8151 5 81076870 81854583 8195 5 81076870
83861633
8152 5 81076870 81859374 8196 5 81076870
83865653
8153 5 81076870 81861368 8197 5 81076870
83865914
8154 5 81076870 81863686 8198 5 81076870
83865920
8155 5 81076870 81916850 8199 5 81076870
83868010
8156 5 81076870 81954891 8200 5 81076870
84019752
8157 5 81076870 81985250 8201 5 81076870
84065912
, 8158 5 81076870 82083752 8202 5 81076870
84086632
8159 5 81076870 82101253 8203 5 81076870
84089603
8160 5 81076870 82143124 8204 5 81076870
84104814
8161 5 81076870 82236318 8205 5 81076870
84105175
8162 5 81076870 82325587 8206 5 81076870
84251635
8163 5 81076870 82427210 8207 5 81076870
84252180
8164 5 81076870 82431853 8208 5 81076870
84253030
8165 5 81076870 82446714 8209 5 81076870
84254208
8166 5 81076870 82446794 8210 5 81076870
84314930
' 8167 5 81076870 82551111 8211 5 81076870 84340523
8168 5 81076870 82552090 8212 5 81076870
84516340
8169 5 81076870 82555641 8213 5 81076870, ,
84706916
8170 5 81076870 82555670 8214 5 81076870
84799488
8171 5 81076870 82556511 8215 5 81076870
84801081
8172 5 81076870 82559047 8216 5 81076870
84824103
8173 5 81076870 82561535 8217 5 81076870
84824203
8174 5 81076870 82610100 8218 5 81076870
84824816
8175 5 81076870 82676822 8219 5 81076870
84825422
8176 5 81076870 82676901 8220 5 81076870
84825763
8177 5 81076870 82883691 8221 5 81076870
84825942
8178 5 81076870 82954942 8222 5 81076870
84843411
8179 5 81076870 82971688 8223 5 81076870
84936441
8180 5 81076870 , 83023965 8224 5 81076870
84936493
8181 5 81076870 83094205 8225 5 81076870
84943705
8182 5 81076870 83146355 8226 5 81076870
169454950
8183 5 81076870 83280630 8227 5 81076870
181522829
8184 5 81076870 83281412 8228 5 81076870
204759879
8185 5 81076870 83400242 8229 5 81076870
209874191
8186 5 81076870 83405797 8230 5 81155197
81157909
8187 5 81076870 83437132 8231 5 81155197
81265937 .
8188 5 81076870 83522252 8232 5 81155197
81265937
8189 5 81076870 83560095 B233 5 81155197
81267485
8190 5 81076870 83560204 8234 5 81155197
81267499
8191 5 81076870 83572400 8235 5 81155197
81274512
8192 5 81076870 83607661 8236 5 81155197
81763618
8193 5 81076870 83745342 8237 5 81155197
81797217
8194 5 81076870 83861275 8238 5 81155197
81800186
203
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chrmnosornal Chnnnosonud
Segment Off. Boundary 1 Boundary2 Segment Cite.
Boundary1 Boundary2
8239 5 81155197 81806213 8281 5 81155197
83861275
8240 5 81155197 81854583 8284 5 81155197
83861633
8241 5 81155197 81859374 8285 5 81155197
83865653
8242 5 81155197 81861368 8286 5 81155197
83865914
8243 5 81155197 81863686 8287 5 81155197
83865920
8244 5 81155197 81916850 8288 5 81155197
83868010
8245 5 81155197 81954891 8289 5 81155197
84019752
8246 5 81155197 81985250 8290 5 81155197
84065912
8747 5 81155197 82083752 8291 5 81155197
84086632
8248 5 81155197 82101251 8292 5 81155197
84089603
8249 5 81155197 82143124 8293 5 81155197
84104814
8250 5 81155197 82236318 8294 5 81155197
84105175
8251 5 81155197 82325587 8295 5 81155197
84251635
8252 5 81155197 82427210 8296 5 81155197
84252180
8253 5 81155197 82431853 6297 5 81155197
84253030
8254 = 5 81155197 82446714 8298 5 81155197
84254208
8255 5 81155197 82446794 8299 5 81155197
84114930
8256 5 81155197 82551111 8300 5 81155197
84340523
8257 5 81155197 82552090 8301 5 81155197
84516340
8258 5 81155197 82555641 8302 5 81155197
84706916
8259 5 81155197 82555670 8303 5 81155197
84799488
82150 5 81155197 82556511 8304 5 81155197
84801081
8261 5 81155197 82559047 8305 5 81155197
84824103
8262 5 81155197 82561535 8306 5 81155197
84824203
8263 5 81155197 82610100 8307 5 81155197
84824816
8264 5 81155197 82676822 8308 5 81155197
84825422
8265 5 81155197 82676901 8309 5 81155197
84825763
8266 5 81155197 82883691 8310 5 81155197
84825942
8267 5 81155197 82954942 8311 5 81155197
84843411
8268 5 81155197 82971688 8312 5 81155197
84936441
8269 5 81155197 83023965 8313 5 81155197
84936493
8270 5 81155197 83094205 8314 5 81155197
84943705
8271 5 81155197 83146355 8315 5 81155197
169454950
8272 5 81155197 83280630 8316 5 81155197
181522829
8273 5 81155197 83281412 8317 5 81155197
204759879
8274 5 81155197 83400242 8318 5 81155197
209874191
8275 5 81155197 83405797 8319 5 81155255
81157909
8276 5 81155197 83437132 8320 5 81155255
81265937
8277 5 81155197 83522252 8321 5 81155255
81265937
8278 5 81155197 83560095 8322 5 81155255
81267485
8279 5 81155197 83560204 8323 5 81155255
81267499
8280 5 81155197 83572400 8324 5 81155255
81274512
8281 5 81155197 83607661 8325 3 81155255
81763618
8282 5 81155197 83745342 8326 5 81155255
81797217
204
CA 02 93 9580 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. Boundaryl Boondary2 Segment Om Bouralmyl Bourolary2
8327 5 81155255 81800186 8371 5 81155255
83745342
8328 5 81155255 81806213 8372 5 81155255
83861275
8329 5 81155255 81854583 8373 5 81155255
83861633
8330 5 81155255 81859374 8374 5 81155255
83865653
8331 5 81155255 81861368 8375 5 81155255
83865914
8332 5 81155255 81863686 8376 5 81155255
83865920
8333 5 81155255 81916850 8377 5 81155255
83868010
8334 5 81155255 81954891 8378 5 81155255
84019752
8335 5 81155255 81985250 8379 5 81155255
84065912
8336 5 81155255 82083752 8380 5 81155255
84086632
8337 5 81155255 82101253 8381 5 81155255
84089603
8338 5 81155255 82143124 8382 5 81155255
84104814
8339 5 81155255 82236318 8383 5 81155255
84105175
8340 5 81155255 82325587 8384 5 81155255
84251635
8341 5 81155255 82427210 8385 5 81155255
84252180
8342 5 81155255 82431853 8386 5 81155255
84253030
8343 5 81155255 82446714 8387 5 81155255
84254208
8344 5 81155255 82416794 8388 5 81155255
84314930
8345 5 81155255 82551111 8389 5 81155255
84340523
8346 5 81155255 82552090 8390 5 81155255
84516340
8347 5 81155255 82555641 8391 5 81155255
84706916
8348 5 81155255 82555670 8392 5 81155255
84799488
8349 5 81155255 82556511 8393 5 81155255
84801081
8350 5 81155255 82559047 8394 5 81155255
84824103
8351 5 81155255 82561535 8395 5 81155255
84824203
8352 5 81155255 82610100 8396 5 81155255
84824816
8353 5 81155255 82676822 8397 5 81155255
84825422
8354 5 81155255 82676901 8398 5 81155255
84825763
8355 5 81155255 82883691 8399 5 81155255
84825942
8356 5 81155255 82954942 8400 5 81155255
84843411
8357 5 81155255 82971688 8401 5 81155255
84936441
8358 5 81155255 83023965 8402 5 81155255
84936493
8359 5 81155255 83094205 8403 5 81155255
84943705
8360 5 81155255 83146355 8404 5 81155255
169454950
8361 5 81155255 83280630 8405 5 81155255
181522829
8362 5 81155255 83281412 8406 5 81155255
204759879
8363 5 81155255 83400242 8407 5 81155255
209874191
8364 5 81155255 83405797 8408 5 81155675
81157909
8365 5 81155255 83437132 8409 5 81155675
81265937
8366 5 81155255 83522252 8410 5 81155675
81265937
8367 5 81155255 83560095 8411 5 81155675
81267485
8368 5 81155255 83560204 8412 5 81155675
81267499
8369 5 81155255 83572400 8413 5 81155675
81274512
8370 5 81155255 83607661 8414 5 81155675
81763618
205
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromencmal Chromosmnal
Segment Or. Boundary 1 Boundary2 Segment an Boundary]
Poundary2
8415 5 81155675 81797217 8459 5 81155675
83607661
8416 5 81155675 81800186 8460 5 81155675
83745342
8417 5 81155675 81806213 8461 5 81155675
83861275
8418 5 81155675 81854583 8462 5 81155675
83861633
8419 5 81155675 81859374 8463 5 81155675
83865653
8420 5 81155675 81861368 8464 5 81155675
83865914
8421 5 81155675 81863686 8465 5 81155675
83865920
8422 5 81155675 81916850 8466 5 81155675
83868010
8423 5 81155675 81954891 8467 5 81155675
84019752
8424 5 81155675 81985250 8468 5 81155675
84065912
8425 5 81155675 82083752 8469 5 81155675
84086632
8426 5 81155675 82101253 8470 5 81155675
84089603
8427 5 81155675 82143124 8471 5 81155675
84104814
8428 5 81155675 82236318 8472 5 81155675
84105175
8429 5 81155675 82325587 8473 5 81155675
84251635
8430 5 81155675 82427210 8474 5 81155675
84252180
8431 5 81155675 82431853 8475 5 81155675
84253030
8432 5 81155675 82416714 8476 5 81155675
84254208
8433 5 81155675 82446794 8477 5 81155675
84314930
8434 5 81155675 82551111 8478 5 81155675
84340523
8435 5 81155675 82552090 8479 5 81155675
84516340
8436 5 81155675 82555641 8480 5 81155675
84706916
8437 5 81155675 82555670 8481 5 81155675
84799488
8438 5 81155675 82556511 8482 5 81155675
84801081
8439 5 81155675 82559047 8483 5 81155675
84824103
8440 5 81155675 82561535 84414 5 81155675
84824203
8441 5 81155675 82610100 8485 5 81155675
84824816
8442 5 81155675 82676822 8486 5 81155675
84825422
8443 5 81155675 82676901 8487 5 81155675
84825763
8444 5 81155675 82883691 8488 5 81155675
84825942
8445 5 81155675 82954942 8489 9 81155675
84843411
8446 5 81155675 82971688 8490 5 81155675
84936441
8447 5 81155675 83023965 8491 5 81155675
84936493
6448 5 81155675 83094205 8492 5 81155675
84943705
8449 5 81155675 83146355 8493 5 81155675
169454950
8450 5 81155675 83280630 8494 5 81155675
181522829
8451 5 81155675 83281412 8495 5 81155675
201759879
8452 5 81155675 83400242 8496 5 81155675
209874191
8453 5 81155675 83405797 8497 5 81156713
81157909
8454 5 81155675 83437132 8498 5 81156713
81265937
8455 5 81155675 83522252 8499 5 81156713
81265937
8456 5 81155675 83560095 8500 5 81156713
81267485
8457 5 81155675 83560204 8501 5 81156713
81267499
8458 5 81155675 83572400 8502 5 81156713
81274512
206
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
-
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary1 Boundar52 Segment Chr. Boundary1 Boundary2
8503 5 81156713 81763618 8547 5 81156713
83572400
8504 5 81156713 81797217 8548 5 81156713
83607661
8505 5 81156713 81800186 8549 5 81156713
83745342
8506 5 81156713 81806213 8550 5 81156713
83861275
8507 5 81156713 81854583 8551 5 81156713
83861633
8508 5 81156713 81859374 8552 5 81156713
83865653
8509 5 81156713 81861368 8553 5 81156713
83865914
8510 5 81156713 81863686 8554 5 81156713
83865920
8511 5 81156713 81916850 8555 5 81156713
83868010
8512 5 81156713 81954891 8556 5 81156713
84019752
8513 5 81156713 81985250 8557 5 81156713
84065912
8514 5 81156713 82083752 8558 5 81156713
84086632
8515 5 81156713 82101253 8559 5 81156713
84089603
8516 5 81156713 82143124 8560 5 81156713
84104814
8517 5 81156713 82236318 8561 5 81156713
84105175
8518 5 81156713 82325587 8562 5 81156713
84251635
8519 5 81156713 82427210 8563 5 81156713
84252180
8520 5 81156713 82431853 8564 5 81156713
84253030
8521 5 81156713 82446714 8565 5 81156713
84254208
8522 5 81156713 82446794 8566 5 81156713
84314930
8523 5 81156713 82551111 8567 5 81156713
84340523
8524 5 81156713 82552090 8568 5 81156713
84516340
8525 5 81156713 82555641 8569 5 81156713
84706916
8526 5 81156713 82555670 8570 5 81156713
64799488
8527 5 81156713 82556511 8571 5 81156713
84801081
8528 5 81156713 82559047 8572 5 81156713
84824103
8529 5 81156713 82561535 8573 5 81156713
84824203
8530 5 81156713 82610100 8574 5 81156713
84824816
8531 5 81156713 82676822 8575 3 81156713
84825422
8532 5 81156713 82676901 8576 5 81156713
84825763
8533 5 81156713 82883691 8577 5 81156713
84825942
8534 5 81156713 62954942 8578 5 81156713
84843411
8535 5 81156713 82971688 8579 5 81156713
84936441
8536 5 81156713 83023965 8580 5 81156713
84936493
8537 5 81156713 83094205 8581 5 81156713
84943705
8538 5 81156713 83146355 8582 5 81156713
169454950
8539 5 81156713 83280630 8581 5 81156713
181522829
8540 5 81156713 83281412 8584 5 81156713
204759879
8541 5 81156713 83400242 8585 5 81156713
209874191
8542 5 81156713 83405797 8586 5 81265211
81265937
8543 5 81156713 83437132 8587 5 81265211
81265937
8544 5 81156713 83529252 8588 5 81265211
81267185
8545 5 81156713 83560095 8589 5 81265211
81267499
8546 5 81156713 83560204 8590 5 81265211
81274512
207
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Doundary1 Boundary2 Segment Chn Boundary I
Boundary2
8591 5 81265211 81763618 8635 5 81265211
83572400
8592 5 81265211 81797217 8636 5 81265211
83607661
8593 5 81265211 81800186 8637 5 . 81265211
83745342
8594 5 81265211 81806213 8638 5 81265211
83861275
8595 5 81265211 81854583 8639 5 81265211
83861633
8596 5 81265211 81859374 8640 5 81265211
83865653
8597 5 81265211 81861368 8641 5 81265211
83865914
8598 5 81265211 81863686 8642 5 81265211
83865920
8599 5 81265211 81916850 8643 5 81265211
83868010
8600 5 81265211 81954891 8644 5 81265211
84019752
8601 5 81265211 81985250 8645 5 81265211
84065912
8602 5 81265211 82083752 8646 5 81265211
84086632
8603 5 81265211 82101253 8647 5 81265211
84089603
8604 5 81265211 82143124 8648 5 81265211
84104814
8605 5 81265211 62236318 0649 5 81265211
84105175
8606 5 81265211 82325587 8650 5 81265211
84251635
8607 5 81265211 82427210 8651 5 81265211
84252180
8608 5 81265211 82431853 8652 5 81265211
84253030
8609 5 81265211 82446714 8653 5 81265211
84254208
8610 5 81265211 82446794 8654 5 81265211
84314930
8611 5 81265211 82551111 8655 5 81265211
84340523
8612 5 81265211 82552090 8656 5 81265211
84516340
8613 5 81265211 82555641 8657 5 81265211
84706916
8614 5 81265211 82555670 8658 5 81265211
84799488
8615 5 81265211 82556511 8659 5 81265211
84801081
8616 5 81265211 82559047 8660 5 81265211
84824103
8617 5 81265211 82561535 8661 5 81265211
84824203
8618 5 81265211 82610100 8662 5 81265211
84824816
8619 5 81265211 82676822 8663 5 81265211
84825422
8620 5 81265211 82676901 8664 5 81265211
84825763
8621 5 81265211 82883691 8665 5 81265211
84825942
8622 5 81265211 82954942 8666 5 81265211
84843411
8623 5 81265211 82971688 8667 5 81265211
84936441
8624 5 81265211 83023965 8668 5 81265211
84936493
8625 5 81265211 83094205 8669 5 81265211
84943705
8626 5 81265211 83146355 8670 5 81265211
169454950
8627 5 81265211 83280630 8671 5 81265211
181522829
8628 5 81265211 83281412 8672 5 81265211
204759879
8629 5 81265211 83400242 8673 5 81265211
209874191
8630 5 81265211 83405797 8674 5 81265354
81265937
8631 5 81265211 83437132 8675 5 81265354
81265937
8632 5 81265211 83522252 8676 5 81265354
81267485
8633 5 81265211 83560095 8677 5 81265354
81274512
8634 5 81265211 83560204 8678 5 81265354
81763618
208
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment at Boundaryl Boundary2 Segment Clu. Boundary1 Boundary2
8679 5 81265354 81797217 8723 5 81265354 83607661
8680 5 81265354 81800186 8724 5 81265354 83745342
8681 5 81265354 81806213 8725 5 81265354 83861275
8682 5 81265354 81854583 8726 5 81265354 83861633
8683 5 81265354 81859374 8727 5 81265354 83865653
8684 5 81265354 81861368 8728 5 81265354 83865914
8685 5 81265354 81863636 8729 5 81265354 83865920
8686 5 81265354 81916850 8730 5 81265354 83868010
8687 5 81265354 81954891 8731 5 81265354 84019752
8688 5 81265354 81985250 8732 5 81265354 84065912
8689 5 81265354 82083752 8733 5 81265354 84086632
8690 5 81265354 82101253 8734 5 61265354 84089603
8691 5 81265354 82143124 8735 5 81265354 84104814
8692 5 81265354 82236318 8736 5 81265354 84105175
8693 5 81265354 82325587 8737 5 81265354 84251635
8694 5 81265354 82427210 8738 5 81265354 84252180
8695 5 81265354 82431853 8739 5 81265354 84253030
8696 5 81265354 82446714 8740 5 81265354 84254208
8697 5 81265354 82446794 8741 5 81265354 84314930
8698 5 81265354 82551111 8742 5 81265354 84340523
8699 5 81265354 82552090 8743 5 81265354 84516340
8700 5 81265354 82555641 8744 5 81265354 84706916
8701 5 81265354 82555670 8745 5 81265354 84799488
8702 5 81265354 82556511 8746 5 81265354 84801081
8703 5 81265354 82559047 8747 5 81265354 84824103
8704 5 81265354 82561535 8748 5 81265354 84824203
8705 5 81265354 82610100 8749 5 81265354 84824816
8706 5 81265354 82676822 8750 5 81265354 84825422
8707 5 81265354 82676901 8751 5 81265354 84825763
8708 5 81265354 82883691 8752 5 81265354 84825942
8709 5 81265354 82954942 8753 5 81265354 84843411
8710 5 81265354 82971688 8754 5 81265354 84936441
8711 5 81265354 83023965 8755 5 81265354 84936493
8712 5 81265354 83094205 8756 5 81265354 84943705
8713 5 81265354 83146355 8757 5 81265354 169454950
8714 5 81265354 83280630 8758 5 81265354 181522829
8715 5 81265354 83281412 8759 5 81265354 204759879
8716 5 81265354 83400242 8760 5 81265354 209874191
8717 5 81265354 83405797 8761 5 81265937 81274512
8718 5 81265354 83437132 8762 5 81265937 81763618
8719 5 81265354 83522252 8763 5- 81265937 81797217
8720 5 81265354 83560095 8764 . 5 81265937 81800186
8721 5 81265354 83560204 8765 5 81265937 81806213
8722 5 81265354 83572400 8766 5 81265937 81854583
209
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (coned.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chi.
Boundary]. Boundary2
8767 5 81265937 81859374 8811 5 81265937
83865653
8768 5 81265937 81861368 8812 5 81265937
83865914
8769 5 81265937 81863686 8813 5 81265937
83865920
8770 5 81265937 81916850 8814 5 81265937
83868010
8771 5 81265937 81954391 8815 5 81265937
84019752
8772 5 81265937 81985250 8816 5 81265937
84065912
8773 5 81265937 82083752 8817 5 81265937
84086632
8774 5 81265937 82101253 8818 5 81265937
84089603
8775 5 81265937 82143124 8819 5 81265937
84104814
8776 5 81265937 82236318 8820 5 81265937
84105175
8777 5 81265937 82325587 8821 5 81265937
84251635
8778 5 81265937 82427210 8822 5 81265937
84252180
8779 5 81265937 12431853 8823 5 81265937
84253030
8780 5 81265937 82446714 8824 5 81265937
84254208
8781 5 81265937 82446794 8825 5 81265937
84314930
8782 5 81265937 82551111 8826 5 81265937
84340523
8783 5 81265937 82552090 8827 5 81265937
84516340
8784 5 81265937 82555641 8828 5 81265937
84706916
8785 5 81265937 82555670 8829 5 81265937
84799488
8786 5 81265937 82556511 8830 5 61265937
84801081
8787 5 81265917 82559047 8831 5 81265937
84824103
8788 5 81265937 82561535 8832 5 81265937
84824203
8789 5 81265937 82610100 8833 5 81265937
84824816
8790 5 81265937 02676822 8834 5 81265937
84825422
8791 5 81265937 82676901 8835 5 81265937
84825763
8792 5 81265937 82883691 8836 5 81265937
84825942
8793 5 81265937 82954942 8837 5 81265937
84843411
8.794 5 81265937 82971688 8838 5 81265937
84936441
8795 5 81265937 83023965 8039 5 81265937
84936493
8796 5 81265937 83094205 8840 5 81265937
84943705
8797 5 81265937 83146355 8841 5 81265937
169454950
, 8798 5 81265937 83280630 8842 5 81265937
181522829
0799 5 81265937 83281412 8843 5 81265937
204759879
8800 5 81265937 83400242 8844 5 81265937
209874191
8801 5 81265937 83405797 8845 5 81273796
81265937
8802 5 81265937 83437132 8846 5 81273796
81274512
8803 5 81265937 83522252 8847 5 81273796
81763618
8804 5 81265937 83560095 8848 5 81273796
81797217
8805 5 81265937 83560204 8849 5 81273796
81800186
8806 5 81265937 83572400 8850 5 81273796
81806213
8807 5 81265937 83607661 8851 5 81273796
81854583
8808 5 81265937 83745342 8852 5 81273796
81859374
8809 5 81265937 83861275 8853 5 81273796
81861368
8810 5 81265937 83861633 8854 5 81273796
81863686
210
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Clnunommnal
Segment Chn Boundary1 Bounday2 Segment Chn Bounden/1 Boundmy2
8855 5 81273796 81916850 8899 5 81273796
83868010
8856 5 81273796 81954891 8900 5 81273796
84019752
8857 5 81273796 81985250 8901 5 81273796
84065912
8858 5 81273796 82083752 8902 5 81273796
84086632
8859 5 81273796 82101253 8903 5 81273796
84089603
8860 5 81273796 82143124 8904 5 81273796
84104814
8861 5 81273796 82236318 8905 5 81273796
84105175
8862 5 81273796 82325587 8906 5 81273796
84251635
8863 5 81273796 82427210 8907 5 81273796
84252180
8864 5 81273796 82431853 8908 5 81273796
84253030
8865 5 81273796 82446714 8909 5 81273796
84254208
8866 5 81273796 82446794 8910 5 81273796
84314930
8867 5 01273796 82551111 8911 5 81273796
84340523
8868 5 81273796 82552090 8912 5 81273796
84516340
8869 5 81273796 82555641 8913 5 81273796
84706916
8870 5 81273796 62555670 8914 5 81273796
84799488
8871 5 81273796 82556511 8915 5 81273796
84801081
8872 5 81273796 82559047 8916 5 81273796
84824103
.
8873 5 81273796 82561535 8917 5 81273796
84824203
8874 5 81273796 82610100 8918 5 81273796
84824816
8875 5 81273796 82676822 8919 5 81273796
84825422
8876 5 81273796 82676901 8920 5 81273796
84825783
8877 5 81273796 82883691 8921 5 81273796
84825942
8978 5 81273796 82954942 8922 5 81273796
84843411
8879 5 81273796 82971688 8923 5 81273796
84936441
8880 5 81273796 83023965 8924 5 81273796
84936493
8881 5 81273796 83094205 8925 5 81273796
84943705
8882 5 81273796 83146355 8926 5 81273796
169454950
8883 5 81273796 83280630 8927 5 81273796
181522829
8884 5 81273796 83281412 8928 5 81273796
204759879
8885 5 81273796 83400242 8929 5 81273796
209874191
8886 5 81273796 83405797 8930 5 81761119
81265937
8887 5 81273796 83437132 8931 5 81761119
81265937
8888 5 81273796 83522252 8932 5 81761119
81267485
8889 5 81273796 83560095 8933 5 81761119
81267499
8890 5 81273796 83560204 8934 5 81761119
81274512
8891 5 81273796. 83572400 8935 5 81761119
81763618
8892 5 81273796 83607661 8936 5 81761119
81797217
8893 5 81273796 83745342 8937 5 81761119
81800186
8894 5 81273796 83861275 8938 5 81761 119
81806213
8895 5 81273796 83861633 8939 5 81761119
81854583
8896 5 81273796 83865653 8940 5 81761119
81859374
8897 5 81273796 83865914 9941 5 81761119
81861368
8898 5 81273796 83865920 8942 5 81761119
81863686
211
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.) .
Chumnosomal Chromosomal
Segment Chr. Boundary 1 Boundary2 Segment Dir.
Boundary 1 Boundary2 .
8943 5 81761119 81916850 8987 5 81761119
83868010
8944 5 81761119 81954891 8988 5 81761119
84019752
8945 5 81761119 81985250 8989 5 81761119
84065912
8946 5 81761119 82083752 8990 5 81761119
84086632
8947 5 81761119 82101253 8991 5 81761119
84089603
8948 5 81761119 82143124 8992 5 81761119
84104814
8949 5 81761119 82236318 8993 5 81761119
84105175
8950 5 81761119 82325587 8994 5 81761119
84251635
8951 5 81761119 82427210 8995 5 81761119
84252180
8952 5 81761119 82431853 8996 5 81761119
84253030
8953 5 81761119 82446714 8997 5 81761119
84254208
8954 5 81761119 82446794 8998 5 81761119
84314930
8955 5 81761119 82551111 8999 5 81761119
84340523
8956 5 81761119 82552090 9000 5 81761119
84516340
8957 5 81761119 82555641 9001 5 81761119
84706916
8958 5 81761119 82555670 9002 5 81761119
84799488
8959 5 81761119 82556511 9003 5 81761119
84801081
8960 5 81761119 82559047 9004 5 81761119
84824103
8961 5 81761119 82561535 9005 5 81761119
84824203
8962 5 81761119 82610100 9006 5 81761119
84824816
8963 5 81761119 82676822 9007 5 81761119
84825422
8964 5 81761119 82676901 9006 9 81761119
84825763
8965 5 81761119 82883691 9009 5 81761119
84825942
8966 5 81761119 82954942 9010 5 81761119
84843411
8967 5 81761119 82971688 9011 5 81761119
84936441
8968 5 81761119 83023965 9012 5 81761119
84936493
8969 5 81761119 83094205 9013 5 81761119
84943705
8970 5 81761119 83146355 9014 5 81761119
169454950
8971 5 81761119 83280630 9015 5 81761119
181522829
8972 5 81761119 83281412 9016 5 81761119
204759879
8973 5 81761119 83400242 9017 5 81761119
209874191
8974 5 81761119 83405797 9018 5 81793777
81265937
8975 5 81761119 83437132 9019 5 81793777
81797217
8976 5 81761119 83522252 9020 5 81793777
81800186
8977 5 81761119 83560095 9021 5 81793777
81806213
8978 5 81761119 83560204 9022 5 81793777
81854583
8979 5 81761119 83572400 9023 5 81793777
81859374
8980 5 81761119 83607661 9024 5 81793777
81861368
8981 5 81761119 83745342 9025 5 81793777
81863686
8982 5 81761119 83861275 9026 5 81793777
81916850
8983 5 81761119 83861633 9027 5 81793777
81954891
8984 5 81761119 83865653 9028 5 81793777
81985250
8985 5 81761119 83865914 9029 5 81793777
82083752
8986 5 81761119 83865920 9030 5 81793777
82101253
= 212
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
-
Table 1 (contd.)
Chronlowinal Chromosomal
Segmag Chr. Boundary! Boundary 2 Segment Chr. Boundary
1 Boundary 2
9031 5 81793777 82143124 9075 5 81793777
84104814
9032 5 81793777 82236318 9076 5 81793777
84105175
9033 5 81793777 82325587 9077 5 81793777
84251635 _
9034 5 81793777 82427210 9078 5 81793777
84252180
9035 5 81793777 82431853 9079 5 81793777
84253030
9036 5 81793777 82446714 9080 5 81793777
84254208
9037 5 81793777 82446794 9081 5 81793777
81314930
9038 5 81793777 82551111 9082 5 81793777
84340523
9039 5 81791777 82552090 9083 5 81793777
84516340
9940 5 81793777 82555641 9084 5 81793777
84706916
9041 5 81793777 82555670 9085 5 81793777
84799488
9042 5 81793777 82556511 9086 5 81793777
84801081
9043 5 81793777 82559047 9087 5 81793777
84824103
9044 5 81793777 82561535 9088 5 81793777
84824203
9045 5 81793777 82610100 9089 5 81793777
84824816
9046 5 81793777 82676822 9090 5 81793777
84825422
9047 5 81793777 82676901 9091 5 81793777
84825763
9048 5 81793777 82883691 9092 5 81793777
84825942
9049 5 81793777 82954942 9093 5 81793777
84843411
9050 5 81793777 82971688 9094 5 81793777
84936441
9051 5 81793777 83023965 9095 5 81793777
84936493
9052 5 81793777 83094205 9096 5 81793777
84943702
9053 5 81793777 83146355 9097 5 81793777
169454950
,
9054 5 81793777 83280630 9098 5 81793777
181522829
9055 5 81793777 83281412 9099 5 81793777
204759879
9056 5 81793777 83400242 9100 5 81793777
209874191
9057 5 81793777 83405797 9101 5 81798893
81265937
9058 5 81793777 83437132 9102 5 81798893
81800186
9059 5 81793777 83522252 9103 5 81798893
81806213
' 9060 5 81793777 83560095 9104 5 81798893 81854583
9061 5 81793777 83560204 9105 5 81798893
81859374
9062 5 .81793777 83572400 9106 5 81798893
81861368
9063 5 81793777 83607661 9107 5 81798893
81863686
9064 5 81793777 83745342 9108 5 81798893
81916850
9065 5 81793777 83861275 9109 5 81798893
81954891
9066 5 81793777 83861633 9110 5 81798893
81985250
9067 5 81793777 83865653 9111 5 81798893
82083752
9068 5 81793777 83865914 9112 5 81798893
82101253 ,
9069 5 81793777 83865920 9113 5 81798893
82143124
9070 5 81793777 83868010 9114 5 81798893
82236316
9071 5 81793777 84019752 9115 5 81798893
82325587
9072 5 81793777 84065912 9116 5 81798893
82427210
9073 5 81793777 84086632 9117 5 81798893
82431853
9074 5 81793777 84089603 9118 5 81798893
12446714
213
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chnmnomng Chromosomal
Segment Chn Boundaly1 Boundary 2 Segment Chn Boundary 1
Boundary2
9119 5 81798893 82446794 9163 5 81798893
84314930
9120 5 81798893 82551111 9164 5 81798893
84340523
9121 5 81798893 82552090 9165 5 81798893
84516340
9122 5 81798893 82555641 9166 5 81798893
84706916
9123 5 81798893 82555670 9167 5 81798893
84799488
9124 5 81798893 82556511 9168 5 81798893
84801081
9125 5 81798893 82559047 9169 5 81798893
84824103
9126 5 81798893 82561535 9170 5 81798893
84824203
9127 5 81798893 82610100 9171 5 81798893
84824816
9128 5 81798893 82676822 9172 5 81798893
84825422
9129 5 81798893 82676901 9173 5 81798893
84825763
9130 5 81798893 82883691 9174 5 81798893
84825942
9131 5 81798893 82954942 9175 5 81798893
84843411
9132 5 81798893 82971688 9176 5 81798893
81936441
9133 5 81798093 83023965 9177 5 81798893
84936493
9134 5 81798893 83094205 9178 5 81798893
84943705
9135 5 81798893 83146355 9179 5 81798893
169454950
9136 5 81798893 83280630 9180 5 81798893
181522829
9137 5 81798893 83281412 9181 5 81798893
204759879
9138 5 81798893 83400242 9182 5 81798893
299874191
9139 5 81798893 83405797 9183 5 81801973
81265937
9140 5 81798893 83437132 9184 5 81801973
81806213
9141 5 81798893 83522252 9185 5 81801973
81854583
9142 5 81798893 83560095 9186 5 81801973
81859374
9143 5 81798893 83560204 9187 5 81801973
81861368
9144 5 81798893 83572400 9188 5 81801973
81863686
9145 5 81798893 83607661 9189 5 81801973
81916850
9146 5 81798893 83745342 9190 5 81801973
81954891
9147 5 81798893 83861275 9191 5 81801973
81985250
9148 5 81798893 83861633 9192 5 81801973
82083752
9149 5 81798893 83865653 9193 5 81801973
82101253
9150 5 81798893 83865914 9194 5 81801973
82143124
9151 5 81798893 83865920 9195 5 81601973
82236318
9152 5 81798893 83868010 9196 5 81801973
82325587
9153 5 81798893 84019752 9197 5 81801973
82427210
9154 5 81798893 81065912 9198 5 81801973
82431853
9155 5 81798893 84086632 9199 5 81801973
82446714
9156 5 81796893 84089603 9200 5 81801973
82446794
9157 5 81798893 84104814 9201 5 81801973
82551111
9158 5 81798893 84105175 9202 5 81801973
82552090
9159 5 81798893 84251635 9203 5 81801973
82555641
9160 5 81798893 84252180 9204 5 81801973
82555670
9161 5 81798893 84253030 9205 5 81801973
82556511
9162 5 81798893 84254208 9206 5 81801973
82559047
214
CA 02 93 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (coned.)
Chromosomal Chromosomal
Segment Chn Boundary1 Boundary2 Segment Chn Boundary1
Boundary 2
9207 5 81801973 82561535 9251 5 81801973
84824203
9208 5 81801973 82610100 9252 5 81801973
84824816
9209 5 81601973 82676822 9253 5 81801973
84825422
9210 5 81801973 82676901 9254 5 81801973
84825763
9211 5 81801973 82883691 9255 5 81801973
84825942
9212 5 81801973 82954942 9256 5 81801973
84843411
9213 5 81801973 82971688 9257 5 81801973
84936441
9214 5 81801973 83023965 9258 5 81801973
84936493
9215 5 81801973 83094205 9259 5 81801973
84943705
9216 5 81801973 83146355 9260 5 81801973
169454950
9217 5 81801973 83280630 9261 5 81801973
181522829
9218 5 81801973 83281412 9262 5 81801973
204759879
9219 5 81801973 83400242 9263 5 81801973
209874191
9220 5 81801973 83405797 9264 5 81854583
81859374
9221 5 81801973 83437132 9265 5 81854583
81861368
9222 5 81801973 83522252 9266 5 81854583
81863686
9223 5 81801973 83560095 9267 5 81854583
81916850
9224 5 81801973 83560204 9268 5 81854583
81954891
9225 5 81801973 83572400 9269 5 81854583
81985250
9226 5 81801973 83607661 9270 5 81854583
82083752
9227 5 81801973 83745342 9271 5 81854583
82101253
9228 5 81801973 83861275 9272 5 81854583
82143124
9229 5 81801973 83861633 9273 5 81854583
82236318
9230 5 81801973 83865653 9274 5 81854583
82325587
9231 5 81801973 83865914 9275 5 81854583
82427210
9232 5 81801973 83865920 9276 5 81854583
82431853
9233 5 81801973 83868010 9277 5 81854583
02446714
9234 5 81801973 84019752 9278 5 81854583
82446794
9215 5 81801973 84065912 9279 5 81854583
82551111
9236 5 81801973 84086632 9280 5 81854583
82552090
9237 5 81801973 84089603 9281 5 81854583
82555641
9238 5 81801973 84104814 9282 5 81854583
82555670
9239 5 81801973 84105175 9283 5 81854583
82556511
9240 5 81801973 84251635 9284 5 81854583
82559047
9241 5 81801973 84252180 9285 5 81854583
82561535
9242 5 81801973 84253030 9286 5 81854583
82610100
9243 5 81801973 84254208 9287 5 81854583
82676822
9244 5 81801973 84314930 9288 5 81854583
82676901
9245 5 81801973 84340523 9289 5 81854583
82883691
9246 5 81801973 84516340 9290 5 81854583
82954942
9247 5 81801973 84706916 9291 5 81854583
82971688
9248 5 81801973 84799488 9292 5 81854583
83023965
9249 5 81801973 84801081 9293 5 81854583
83094205
9250 5 81801973 84824103 9294 5 81854583
83146355
215
CA 02 9 3 958 0 2016-08-11
WO 2015/127248
PCT/US2015/016877
,
Table 1 (contd.)
Chromosomal Clumnosomal
Segnent Chr. Boundary 1 Boundary2 Segment Chr Boundaty1
Boundary 2
9295 5 81854583 83280610 9339 5 81854583 181522829
9296 5 81854583 83281412 9340 5 81854583 204759879
9297 5 81854583 83400242 9341 5 81854583 209874191
9298 5 81854583 83405797 9342 5 81858527 81859374
9299 5 81854583 83437132 9343 5 81858527 81861368
9300 5 81854583 83522252 9344 5 81858527 81863686
9301 _ 5 81854583 83560095 9345 5 81858527 81916850
9302 5 81854583 83560204 9346 5 81858527 81954891
9303 5 81854583 83572400 9347 5 81858527 81985250
9304 5 81854583 83607661 9348 5 81858527 82083752
9305 5 81854583 83745342 9349 5 81858527 82101253
9306 5 81854583 83861275 9350 5 81858527 82143124
9307 5 81854583 83861633 9351 5 81858527 82236318
9308 5 81854583 83865653 9352 5 81858527 82325587
9309 5 81854583 81865914 9353 5 81858527 82427210
9310 5 81854583 83865920 9354 5 81858527 82431853
9311 5 81854583 81868010 9155 5 81858527 82446714
9312 5 81854583 64019752 9356 5 81858527 82446794
9313 5 81854583 84065912 9357 5 81858527 82551111
9314 5 81854583 84086632 9358 5 81858527 82552090
9315 5 81854583 84089603 9359 5 81858527 82555641
9316 5 81854583 84104814 9360 5 81850527 82555670
9317 5 81854583 84105175 9361 5 81858527 82556511
9318 5 81854583 84251635 9362 5 81858527 82559047
9319 5 81854583 84252180 9363 5 81858527 82561535
9320 5 81854583 84253030 9364 5 81858527 82610100
9321 5 81854583 84254208 9365 5 81858527 82676822
9322 5 81854583 84314930 9366 5 81858527 82676901
9323 5 81854583 84340523 9367 5 81858527 82883691
9324 5 81854583 84516340 9368 5 81858527 82954942
. 9325 5 81854583 84706916 9369 5 81858527 82971688
9326 5 81854583 04799488 9370 5 81858527 03023965
9327 5 81854583 84801081 9371 5 81858527 83094205
9328 5 81854583 84824103 9372 5 81858527 83146355
9329 5 81854583 84824203 9373 5 81858527 83280630
9330 5 81854583 84824816 9374 5 81858527 83281412
9331 5 81854583 84825422 9375 5 81858527 83400242
9332 5 81854583 84825763 9376 5 81858527 83405797
9333 5 81854583 84825942 9377 5 81858527 83437132
9334 5 81854583 84843411 9378 5 81858527 83522252
9335 5 81854583 84936441 9379 5 81858527 83560095
9336 5 81854583 84936493 9380 5 81858527 83560204
9337 5 81854583 84943705 9381 5 61858527 83572400
9338 5 81854583 169454950 9382 5 81858527 83607661
216
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary1 Boundary2 Segment ChL Boundary! Boundary2
9383 5 81858527 83745342 9427 5 81859618
82101253
9384 5 81858527 83861275 9428 5 81859618
82143124
9385 5 81858527 83861633 9429 5 81859618
82236318
9386 5 81858527 83865653 9430 5 81859618
82325587
9387 5 81858527 83865914 9431 5 81859618
82427210
9388 5 81858527 83865920 9432 5 81859618
82431853
9389 5 81858527 83868010 9433 5 81859618
82446714
9390 5 81858527 84019752 9434 5 81859618
82446794
9391 5 81858527 84065912 9435 5 81859618
82551111
9392 5 81858527 84086632 9436 5 81859618
82552090
9393 5 81858527 84089603 9437 5 81859618
82555641
9394 5 81858527 84104814 9438 5 81859618
82555670
9395 5 81858527 84105175 9439 5 81859618
82556511
9396 5 81858527 84251635 9440 5 81859618
82559047
9397 5 81858527 84252180 9441 5 81859618
82561535
9398 5 81858527 84253030 9442 5 81859618
82610100
9399 5 81858527 84254208 9443 5 81859618
82676822
9400 5 81858527 84314930 9444 5 81859618
82676901
9401 5 81858527 84340523 9445 5 81859618
82883691
9402 5 81858527 84516340 9446 5 81859618
82954942
9403 5 81858527 84706916 9447 5 81859618
82971688
9404 5 81858527 84799488 9448 5 81859618
83023965
9405 5 81858527 84801081 9449 5 81859618
83094205
9406 5 81858527 84824103 9450 5 81859618
83146355
9407 5 81858527 84824203 9451 5 81859618
83280630
9408 5 81858527 84824816 9452 5 81859618
83281412
9409 5 81858527 84825422 9453 5 81859618
83400242
9410 5 81858527 84825763 9454 5 81859618
83405797
9411 5 81858527 84825942 9455 5 81859618
83437132
9412 5 81858527 84843411 9456 5 81859618
83522252
9413 5 81858527 84936441 9457 5 81859618
83560095
9414 5 81858527 84936493 9458 5 81859618
83560204
9415 5 81858527 84943705 9459 5 81859618
83572400
9416 5 81858527 169454950 9460 5 81859618
83607661
9417 5 81858527 181522829 9461 5 81859618
83745342
9418 5 81858527 204759879 9462 5 81859618
83861275
9419 5 81858527 209874191 9463 5 81859618
83861633
9420 5 8185961/3 81265937 9464 5 81859618
83865653
9421 5 81859618 81861368 9465 5 81859618
83865914
9422 5 81859618 81863686 9466 5 81859618
83865920
9423 5 81859618 81916850 9467 5 81859618
83868010
9424 5 81859618 81954891 9468 5 81859618
84019752
9425 5 81859618 81985250 9469 5 81859618
84065912
9426 5 81859618 82083752 9470 5 81859618
84086632
217
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Clic Boundaryl Boundary2 Segment Chr. Boundaryl
Boundary 2
9471 5 81859618 84089603 9515 5 81863099
82555670
9472 5 81859618 84104814 9516 5 81863099
82556511
9473 5 81859618 84105175 9517 5 81863099
82559047
9474 5 81859618 84251635 9518 5 81863099
82561535
9475 5 81859618 84252180 9519 5 81863099
82610100
9476 5 81859618 84253030 9520 5 81863099
82676822
9477 5 81859618 84254208 9521 5 81863099
82676901
9478 5 81859618 84314930 9522 5 81863099
82883691
9479 5 81859618 84340523 9523 5 81863099
82954942
9480 5 81859618 84516340 9524 5 81863099
82971688
9481 5 81859618 84706916 9525 5 81863099
83023965
9482 5 81859618 84799488 9526 5 81863099
83094205
9483 5 81859611 84801081 9527 5 81863099
83146355
9484 5 81859618 84824103 9528 5 81863099
83280630
9485 5 81859618 84824203 9529 5 81863099
83281412
9486 5 81859618 84824816 9530 5 81863099
83400242
9487 5 81859618 84825422 9531 5 81863099
83405797
9488 5 81859618 84825763 9532 5 81863099
83437132
9489 5 81859618 84825942 9533 5 81863099
83522252
9490 5 81859618 84843411 9534 5 81863099
83560095
9491 5 81859618 84936441 9535 5 81863099
83560204
9492 5 81859618 84936493 9536 5 81863099
83572400
9493 5 81859618 84943705 9537 5 81863099
83607661
9494 5 81859618 169454950 9538 5 81863099
83745342
9495 5 81859618 181522829 9539 5 81863099
83861275
9496 5 81859618 204759879 9546 5 81863099
83861633
9497 5 81859618 209874191 9541 5 81863099
83865653
9498 5 81863099 81265937 9542 5 81863099
83865914
9499 5 81863099 81863686 9543 5 81663099
83865920
9500 5 81863099 81916850 9544 5 81863099
83868010
9501 5 81863099 81954891 9545 5 81863099
84019752
9502 5 81863099 81985250 9546 5 81863099
84065912
9503 5 81863099 82083752 9547 5 81863099
84086632
9504 5 81863099 82101253 9548 5 81863099
84089603
9505 5 81863099 82143124 9549 5 81863099
84104814
=
9506 5 81863099 82236318 9550 5 81863099
84105175
9507 5 81863099 82325587 9551 5 81863099
84251635
9508 5 81863099 82427210 9552 5 81863099
84252180
9509 5 81863099 82431853 9553 5 81863099
84253030
9510 5 81863099 82446714 9554 5 81863099
84254208
9511 5 81863099 82446794 9555 5 81863099
84314930
9512 5 81863099 82551111 9556 5 ' 81863099
84340523
9513 5 81863099 82552090 9557 5 81863099
84516340
9514 5 011163099 82555641 9558 5 81863099
84706916
218
CA 02 9 3 95 8 0 2 016 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment ain I3mmulary1 Boundary2 Segment Chn Boundary 1
Boundary 2
9559 5 81863099 84799488 9603 5 81914498 83146355
9560 5 81863099 84801081 9604 5 81914498 83280630
9561 5 81863099 84821103 9605 5 81914498 83281412
9562 5 81863099 84824203 9606 5 81914498 83400242
9563 5 81863099 84824816 9607 5 81914498 83405797
9564 5 81863099 84825422 9608 5 81914498 83437132
9565 5 81863099 84825763 9609 5 81914498 83522252
9566 5 81863099 84825942 9610 5 81914498 83560095
9567 5 81863099 84843411 9611 5 81914498 83560204
9568 5 81863099 84936441 9612 5 81914498 83572400
,
9569 5 81863099 84936493 9613 5 81914498 83607661
9570 5 81863099 84943705 9614 5 81914498 83745342
9571 5 81863099 169454950 9615 5 81914498 83861275
9572 5 81863099 181522829 9616 5 81914498 83861633
9573 5 81863099 204759879 9617 5 81914498 83865653
9574 5 81863099 209874191 9618 5 81914498 83865914
9575 5 81914198 81265937 9619 5 81914498 83865920
9576 5 81914498 81916850 9620 5 81914498 83868010
9577 5 81914498 81954891 9621 5 81914498 84019752
9578 5 81914498 81985250 9622 5 81914498 84065912
9579 5 81914498 82083752 9623 5 81914498 84086632
9580 5 81914498 82101253 9624 5 81914498 84089603
9581 5 81914498 82143124 9625 5 81914498 84104814
9582 5 81914498 82236318 9626 5 81914498 84105175
9583 5 81914498 82325587 9627 5 81914498 84251635
9584 5 81914498 82427210 9628 5 81914498 84252180
9585 5 81914498 82431853 9629 5 81914498 84253030
9586 5 81914498 82446714 9630 5 81914498 84254208
9587 5 81914498 82446794 9631 5 81914498 84314930
9588 5 81914498 82551111 9632 5 81914498 84340523
9589 5 81914498 82552090 9633 5 81914498 84516340
9590 5 81914498 82555641 9634 5 81914498 84706916
9591 5 81914498 82555670 9635 5 81914498 84799488
9592 5 81914498 82556511 9636 5 81914498 84801081
9593 5 81914498 82555047 9637 5 81914498 84824103
9594 5 81914498 82561535 9638 5 81914498 84824203
9595 5 81914498 82610100 9639 5 81914498 84824816
9596 5 81914498 82676822 9640 5 81914498 84825422
9597 5 81914498 82676901 9641 5 81914498 84825763
9598 5 81914498 82883691 9642 5 81914498 84825942
9599 5 81914498 82954942 9643 5 81914498 84843411
9639) 5 81914498 82971688 9644 5 81914498 84936441
9601 5 81914498 83023965 9645 5 81914498 84936493
9602 5 81914498 83094205 9646 5 81914498 84943705
219
CA 02 93 9580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segtnent Chr. Boundary 1 Boundary 2 Szymen1 Chn Boundaryl
Boondary2
9647 5 81914498 169454950 9691 5 81950191 83861633
9648 5 81914498 181522829 9692 5 81950191 83865653
9649 5 81914498 204759879 9693 5 81950191 83865914
9650 5 81914498 209874191 9694 5 81950191 83865920
9651 5 81950191 81265937 9695 5 81950191 83868010
9652 5 81950191 81954891 9696 5 81950191 84019752
9653 5 81950191 81985250 9697 5 81950191 84065912
9654 5 81950191 82083752 9698 5 81950191 84086632
=
9655 5 81950191 82101253 9699 5 81950191 84089603
9656 5 81950191 82143124 9700 5 81950191 84104814
9657 5 81950191 82236318 9701 5 81950191 84105175
9658 5 81950191 82325587 9702 5 81950191 84251635
9659 5 81950191 82427210 9703 5 81950191 84252180
9660 5 81950191 82431853 9704 5 81950191 84253030
9661 5 81950191 82446714 9705 5 81950191 84254208
9662 5 81950191 82446794 9706 5 81950191 84314930
9663 5 81950191 82551111 9707 5 81950191 84340523
9664 5 81950191 82552090 9708 5 81950191 84516340
9665 5 81950191 82555641 9709 5 81950191 84706916
9666 5 81950191 82555670 9710 5 81950191 84799488
9667 5 81950191 82556511 9711 5 81950191 84801081
9668 5 81950191 82559047 9712 5 81950191 84824103
9669 5 81950191 82561535 9713 5 81950191 84824203
9670 5 81950191 82610100 9714 5 81950191 84824816
9671 5 81950191 82676822 9715 5 81950191 84825422
9672 5 81950191 82676901 9716 5 81950191 84825763
9673 5 81950191 82883691 9717 5 81950191 84825942
9674 5 81950191 82954942 9718 5 81950191 84843411
9675 5 81950191 82971688 9719 5 81950191 84936441
9676 5 81950191 83023965 9720 5 81950191 84936493
9677 5 81950191 83094205 9721 5 81950191 84943705
9678 5 81950191 83146355 9722 5 81950191 169454950
9679 5 81950191 83280630 9723 5 81950191 181522829
9680 5 81950191 83281412 9724 5 81950191 204759879
9681 5 81950191 83400242 9725 5 81950191 209874191
9682 5 81950191 83405797 9726 5 81951639 81265937
9683 5 81950191 83437132 9727 5 81951639 81954891
9684 5 81950191 83522252 9728 5 81951639 81985250
9685 5 81950191 83560095 9729 5 81951639 82083752
9686 5 81950191 83560204 9730 5 81951639 82101253
9687 5 81950191 83572400 9731 5 81951639 82143124
9688 5 81950191 83607661 9732 5 81951639 82236318
9689 5 81950191 83745342 9733 5 81951639 82325587
9690 5 81950191 83861275 9734 5 81951639 82427210
220
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 0 8 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Clironiosomal Chromosmnal
Segment Or. Bountlary1 Bounchny2 Segment Chr. Boundary1 Boundmy2
9935 5 61951639 82431853 9779 5 81951639 84253030
9736 5 81951639 82446714 9780 5 81951639 84254208
9737 5 81951639 82446794 9781 5 81951639 84314930
9738 5 81951619 82551111 9782 5 81951639 84340523
9739 5 81951639 82552090 9783 5 81951639 84516340
9740 5 81951639 82555641 9784 5 81951639 84706916
9741 5 81951639 82555670 9785 5 81951639 84799488
9742 5 81951639 82556511 9786 5 01951639 84801081
9743 5 81951639 82559047 9787 5 81951639 84824103
9744 5 88951639 82561535 9788 5 81951639 84824203
9745 5 81951639 82610100 9789 5 81951639 84824816
9746 5 81951639 82676822 9790 5 81951639 84825422
9747 5 81951639 82676901 9791 5 81951639 84825763
9748 5 81951639 82883691 9792 5 81951639 84825942
9749 5 81951639 82954942 9793 5 81951639 84843411
9750 5 81951639 82971688 9794 5 81951639 84936441
9751 5 81951639 83023965 9795 5 81951639 84936493
9752 5 81951639 83094205 9796 5 81951639 84943705
9753 5 81951639 83146355 9797 5 81951639 169454950
9754 5 81951639 82280630 9798 5 81951639 181522829
9755 5 81951639 83281412 9799 5 81951639 204759879
9756 5 81951639 83400242 9800 5 81951639 209874191
9757 5 81951639 83405797 9801 5 81984901 81265937
9758 5 81951639 83437132 9802 5 81984901 81985250
9759 5 81951639 83522252 9803 5 81984901 82083752
9760 5 81951639 83560095 9804 5 81984901 82101253
9761 5 81951639 83560204 9805 5 81984901 82143124
9762 5 81951639 83572400 9806 5 81984901 82236318
9763 5 81951639 83607661 9807 5 81984901 82325587
9764 5 81951639 83745342 9808 5 81984901 82427210
9765 5 81951639 83861275 9809 5 81984901 82431853
9766 5 81951639 83861633 9810 5 81984901 82446714
9767 5 81951639 83865653 9811 5 81984901 82446794
9768 5 81951639 83865914 9812 5 81984901 82551111
9769 5 81951639 83865920 9813 5 81984901 82552090
9770 5 81951639 83868010 9814 5 81984901 82555641
9771 5 81951619 84019752 9815 5 81984901 82555670
9772 5 81951639 84065912 9816 5 81984901 82556511
9773 5 81951639 84086632 9817 5 81984901 82559047
9774 5 81951639 84089603 9818 5 81984901 82561535
9775 5 81951639 84104814 9819 5 81984901 82610100
9776 5 81951639 84105175 9820 5 81984901 82676822
9777 5 81951639 84251635 9821 5 81984901 82676901
9778 5 81951639 84252180 9822 5 81984901 82883691
221
CA 02 9 3 95 8 0 2 0 16 -013-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Cht Boundary 1 Bouneary2 Segment CM Boundary1
Boundary2
9823 5 81984901 82954942 9867 5 81984901
84843411
9824 5 81984901 82971688 9868 5 81984901
84936441
9825 5 81984901 83023965 9869 5 81984901
84936493
9826 5 81984901 83094205 9870 5 81984901
84943705
9827 5 81984901 83146355 9871 5 81984901
169454950
9828 5 81984901 83280630 9872 5 81984901
181522829
9829 5 81984901 83281412 91173 5 81984901
204759879
9830 5 81984901 83400242 9874 5 81984901
209874191
9831 5 81984901 83405797 9875 5 82083639
81265937
9832 5 81984901 83437132 9876 5 82083639
82083752
9833 5 81984901 83522252 9877 5 82083639
82101253
9834 5 81984901 83560095 9878 5 82083639
82143124
9635 5 81984901 83560204 9179 5 82083639
82236318
9836 5 81984901 83572400 9880 5 82083639
82325587
9837 5 81984901 83607661 9881 5 82083639
82427210
9838 5 81984901 83745342 9882 5 82083639
82431853
9839 5 81984901 83861275 9883 5 82083639
82446714
9840 5 81984901 83861633 9884 5 82083639
82446794
9841 5 81984901 83865653 9885 5 82083639
82551111
9842 5 81984901 83865914 9886 5 82083639
82552090
9843 5 81984901 83865920 9887 5 82083639
82555641
9844 5 81984901 83868010 9888 5 82083639
82555670
9845 5 81984901 84019752 9889 5 82083639
82556511
9846 5 81984901 84065912 9890 5 82083639
82559047
9847 5 81984901 84086632 9891 5 82083639
82561535
9848 5 81984901 84089603 .9892 5 82083639
82610100
9849 5 81984901 84104814 9893 5 82083639
82676822
9850 5 81984901 84105175 9894 5 82083639
82676901
9851 5 81984901 84251635 9895 5 82083639
82883691
9852 5 81984901 84252180 9896 5 82083639
82954942
9853 5 81984901 84253030 9897 5 82083639
82971688
9854 5 81984901 84254208 9898 5 82083639
83023965
9855 5 81984901 84314930 9899 5 82083639
83094205
9856 5 81984901 84340523 9900 5 82083639
83146355
9857 5 81984901 84516340 9901 5 82083639
83280630
9858 5 81984901 84706916 9902 5 82083639
83281412
9859 5 81984901 84799488 9903 5 82083639
83400242
9860 5 81984901 84801081 9904 5 82083639
83405797
9861 5 81984901 84824103 9905 5 82083639
83437132
9862 5 81984901 84824203 9906 5 82083639
83522252
9863 5 81984901 84824816 9907 5 82083639
83560095
9864 5 81984901 84825422 9908 5 82083639
83560204
9865 5 81984901 84825763 9909 5 82083639
83572400
9866 5 81984901 84825942 9910 5 82083639
83607661
= 222
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosmnal
Segment Chn Boundmyl Boundary2 Segment Chr. Boundary1 Boundary2
9911 5 82083639 83745342 9955 5 82083752
82446714
9912 5 82083639 83861275 9956 5 82083752
82446794
9913 5 82083639 83861633 9957 5 82083752
82551111
9914 5 82083639 83865653 9958 5 82083752
82552090
9915 5 82083639 83865914 9959 5 82083752
82555641
9916 5 82083639 83865920 9960 5 82083752
82555670
9917 5 82083639 83868010 9961 5 82083752
82556511
9918 5 82083639 84019752 9962 5 82083752
82559047
9919 5 82083639 84065912 9963 5 82083752
82561535
9925 5 82083639 84086632 9964 5 02083752
82610100
9921 5 82083639 84089603 9965 5 82083752
82676822
9922 5 82083639 84104814 9966 5 82083752
82676901
9923 . 5 82083639 84105175 9967 5 82083752
82883691
9924 5 82083639 84251635 9968 5 82083752
82954942
9925 5 82083639 84252180 9969 5 82083752
82971688
9926 5 82083639 84253030 9970 5 82083752
83023965
9927 5 82083639 84254208 9971 5 82083752
83094205
9928 5 82083639 84314930 9972 5 82083752
83146355
9929 5 82083639 84340523 9973 5 82003752
83280630
9930 5 82083639 84516340 9974 5 82083752
83281412
9931 5 82083639 84706916 9975 5 82083752
83400242
9932 5 82083639 84799488 9976 5 82083752
83405797
9933 ' 5 82083639 84801081 9977 5 82083752 83437132
9934 5 82083639 84824103 9978 5 82083752
83522252
9935 5 82083639 84824203 9979 5 82083752
83560095
5936 5 82083639 84824816 9980 5 82083752
83560204
9937 5 82083639 84825422 9981 5 82083752
83572400
9938 = 5 82083639 84825763 9982 5 82083752
83607661
9939 5 82083639 84825942 = 9983 5 82083752
83745342
9940 5 82083639 84843411 9984 5 82083752
83861275
9941 5 82083639 84936441 9985 5 82083752
83861633
9942 5 82083639 84936493 9986 5 82083752
83865653
9943 5 82083639 84943705 9987 5 82083752
83865914
9944 5 82083639 169454950 9988 5 82083752
83865920
9945 5 82083639 181522829 9989 5 82083752
83868010
9946 5 82083639 204759879 9990 5 82083752
84019752
9947 5 82083639 209874191 9991 5 82083752
84065912
9948 5 82083752 81265937 9992 5 82083752
84086632
9949 5 82083752 82137780 9993 5 82083752
84089603
9950 5 82083752 82143124 9994 5 82083752
84104814
9951 5 82083752 82236318 9995 5 82083752
84105175
9952 5 82083752 82325587 9996 5 82083752
84251635
9953 5 82083752 82427210 9997 5 82083752
84252180
9954 5 82083752 82431853 9998 5 82083752
84253030
223
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chrmnosmnal
Segment Chr. Boundary1 Boun66ry2 Segment Chr Boundary 1
Boundmy2
9999 5 820133752 84254208 10043 5 82137780 83146355
10000 5 82083752 84314930 10044 5 82137780 83280630
10001 5 82083752 84340523 10045 5 82137780 83281412
10002 5 82083752 84516340 10046 5 82137780 83400242
10003 5 82083752 84706916 10047 5 82137780 83405797
,
,
10004 5 82083752 84799488 10048 5 82137780 83437132
= 10005 5 82083752 84801081 ' 10049
5 82137780 83522252
10006 5 82083752 84824103 10050 5 82137780 83560095
10007 5 82083752 84824203 10051 5 82137780 83560204
10008 5 82083752 84824816 10052 5 82137780 83572400
. 10009 5 , 82083752 84825422 10053 5 82137780
83607661
10010 5 82083752 84825763 10054 5 82137780 83745342
10011 5 82083752 84825942 10055 5 82137780 83861275
10012 5 82083752 84843411 10056 5 82137780 83861633
10013 5 82083752 84936441 10057 5 82137780 83865653
10014 5 82083752 84936493 10058 5 82137780 83865914
10015 5 82083752 84943705 10059 5 82137780 83865920
10016 5 82083752 169454950 10060 5 82137780 83868010
10017 5 82083752 181522829 10061 5 82137780 84019752
10018 5 82083752 204759879 10062 5 82137780 84065912
10019 5 82083752 209874191 10063 5 82137780 84086632
10020 5 82137780 81265937 10064 5 82137780 84089603
10021 5 82137780 82143124 10065 5 82137780 84104814
10022 5 82137780 82236318 10066 5 82137780 84105175
10023 5 82137780 82325587 10067 5 82137780 84251635
10024 5 82137780 82427210 10068 5 82137780 84252180
10025 5 82137780 82431853 10069 5 82137780 84253030
10026 5 82137780 82446714 10070 5 82137780 , 84254208
10027 5 82137780 82446794 10071 5 82137780 84314930
10028 5 82137780 82551111 10072 5 82137780 84340523
10029 5 82137780 82552090 10073 5 82137780 84516340
10030 5 82137780 82555641 10074 5 82137780 84706916
10031 5 82137780 82555670 10075 5 82137780 84799488
10032 5 82137780 82556511 10076 5 82137780 84801081
10033 5 82137780 82559047 10077 5 82137780 84824103
10034 5 82137780 82561535 10078 5 82137780 84824203
10035 5 82137780 82610100 10079 5 82137780 84824816
10036 5 82137780 82676822 10080 5 82137780 84823477
10037 5 82137780 82676901 10081 5 82137780 84825763
10038 5 82137780 82883691 10082 5 82137780 84825942
10039 5 82137780 82954942 10083 5 82137780 84843411
10040 5 82137780 82971688 10084 5 82137780 84936441
10041 5 82137780 83023965 10085 5 82137780 84936493
10042 5 82137780 83094205 10086 5 82137780 84943705
224
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Cho. Bnundary1 Boundaly2 Segment Chr. Boundary! Boundmy2
10087 5 82137780 169454950 10131 5 82139338
83868010
10088 5 82137780 181522829 10132 5 82139338
84019752
10089 5 82137780 204759879 10133 5 82139338
84065912
10090 5 82137780 209874191 10134 5 82139338
84086632
10091 5 82139338 81265937 10135 5 82139338
84089603
10092 5 82139338 82143124 10136 5 82139338
84104814
10093 5 82139338 82236318 10137 5 82139338
84105175
10094 5 82139338 82325587 10138 5 62139338
84251635
10095 5 82139338 82427210 10139 5 82139338
84252180
10096 5 82139338 82431853 10140 5 82139338
84253030
10097 5 82139338 82446714 10141 5 82139338
84254208
10098 5 82139338 82446794 10142 5 82139338
84314930
10099 5 82139338 82551111 10143 5 82139338
84340523
10100 5 82139338 82552090 10144 5 82139338
84516340
10101 5 82139338 82555641 10145 5 82139338
84706916
10102 5 82139338 82555670 10146 5 82139338
84799488
10103 5 82139338 82556511 10147 5 82139338
84801081
10104 5 82139338 62559047 10148 5 82139338
84824103
10105 5 82139338 82561535 10149 5 82139338
84824203
10106 5 82139338 82610100 10150 5 82139338
84824816
10107 5 82139338 82676822 10151 5 82139338
84825422
10108 5 82139338 82676901 10152 5 82139338
84825763
10159 5 82139338 82883691 10153 5 82139338
84825942
10110 5 82139338 82954942 10154 5 82139338
84843411
10111 5 82139338 82971688 10155 5 82139338
84936441
10112 5 82139338 83023965 10156 5 82139338
84936493
10113 5 82139338 83094205 10157 5 82139338
84943705
10114 5 82139338 83146355 10158 5 82139336
169454950
10115 5 82139338 83280630 10159 5 82139338
181522829
10116 5 82139338 83281412 10160 5 82139338
204759879
10117 5 82139338 83400242 10161 5 82139338
209874191
10118 5 82139338 83405797 10162 5 82234311
81265937
10119 5 82139338 83437132 10163 5 82234311
82236318
10120 5 82139338 83522252 10164 5 82234311
82325587
10121 5 82139331 83560095 10165 5 82234311
82427210
10122 5 82139338 83560204 10166 5 82234311
82431853
10123 5 82139338 83572400 10167 5 82234311
82446714
10124 5 82139338 83607661 10168 5 82234311
82446794
10125 5 82139338 83745342 10169 5 82234311
82551111
10126 5 82139338 83861275 10170 . 5, 82234311
82552090
10127 5 82139338 83661633 10171 5 82234311
82555641
10128 5 82139330 83865653 10172 5 82234311
82555670
10129 5 82139338 83865914 10173 5 82234311
82556511
10130 5 82139338 83865920 10174 5 82234311
82559047
. 225
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 0 8 ¨ 11
WO 2015/127248 PCT/US2015/016877
Table 1 (cont'd.)
Chnnnosornal Chromosomal
Segment Chr. Boundaryl Boundary2 Segment Chr. Boundary 1
Boundary2
10175 5 82234311 82561535 10219 5 82234311 84824203
10176 5 82234311 82610100 10220 5 82234311 84824816
10177 5 82234311 82676822 10221 5 82234311 84825422
10178 5 82234311 82676901 10222 5 82234311 84825763
10179 5 82234311 82883691 10223 5 82234311 84825942
10180 5 82234311 82954942 10224 5 82234311 84843411
10181 5 82234311 82971688 10225 5 82234311 84936441
10182 5 82234311 83023965 10226 5 82234311 84936493
10183 5 82234311 83094205 10227 5 82234311 84943705
10184 5 82234311 83146355 10228 5 82234311 169454950
10185 5 82234311 83280630 10229 5 82234311 181522829
10186 5 82234311 83281412 10230 5 82234311 204759879
10187 5 82234311 83400242 10231 5 82234311 209874191
10188 5 82234311 83405797 10232 5 82236318 81265937
10189 5 82234311 83437132 10233 5 82325587 82423451
10190 5 82234311 83522252 10234 5 82325587 82427210
10191 5 82234311 83560095 10235 5 82325587 82431853
10192 5 E2234311 83560204 10236 5 82325587 82446714
10193 5 82234311 83572400 10237 5 82325587 82446794
10194 5 82234311 83607661 10238 5 82325587 82551111
10195 5 82234311 83745342 10239 5 82325587 82552090
10196 5 82234311 83861275 10240 5 82325587 82555641
10197 5 82234311 83861633 10241 5 82325587 82555670
10198 5 82234311 83865653 10242 5 82325587 82556511
10199 5 82234311 83865914 _ 10243 5 82325587
82559047
10200 5 82234311 83865920 10244 5 82325587 82561535
10201 5 82234311 83868010 10245 5 82325587 82610100
10202 5 82234311 84019752 10246 5 82325587 82676822
10203 5 82234311 84065912 10247 5 82325587 82676901
10204 5 82234311 84086632 10248 5 82325587 82883691
10205 5 82234311 84089603 10249 5 82325587 82954942
10206 5 82234311 84104814 10250 5 82325587 82971688
10207 5 82234311 84105175 10251 5 82325587 83023965
10208 5 82234311 84251635 10252 5 82325587 83094205
10209 5 82234311 84252180 10253 5 82325587 83146355
10210 5 82234311 84253030 10254 5 82325587 83280630
10211 5 82234311 84254208 10255 5 82325587 83281412
10212 5 82234311 84314930 10256 5 82325587 83400242
10213 5 82234311 84340523 10257 5 82325587 83405797
10214 5 82234311 84516340 10258 5 82325587 83437132
10215 5 82234311 84706916 10259 5 82325587 83522252
10216 5 82234311 84799488 10260 5 82325587 83560095
10217 5 82234311 84801081 10261 5 82325587 83560204
10218 5 82234311 84824103 10262 5 82525587 83572400
226
CA 02 939580 2 0 16-08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Boundary 2 Segment Chr. Boundary
1 Boundary 2
10263 5 82325587 83607661 10307 5 82423451 82555641
10264 5 82325587 83745342 10308 5 82423451 82555670
10265 5 82325587 83861275 10309 5 82423451 82556511
10266 5 82325587 83861633 10310 5 82423451 82559047
10267 5 82325587 83865653 10311 5 82423451 82561535
10268 5 82325587 83865914 10312 5 82423451 82610100
10269 5 82325587 83865920 10313 5 82423451 82676822
10270 5 82325587 83868010 10314 5 82423451 82676901
10271 5 82325587 84019752 10315 5 82423451 82883691
10272 5 82325587 84065912 10316 5 82423451 82954942
10273 5 82325587 84086632 10317 5 82423451 82971688
10274 5 82325587 84089603 10318 5 82423451 83023965
10275 5 82325587 84104814 10319 5 82423451 83094205
10276 5 82325587 84105175 10320 5 82423451 83146355
10277 5 82325587 84251635 10321 5 82423451 83280630
10278 5 82325587 84252180 10322 5 82423451 83281412
10279 5 82325587 84253030 10323 5 82423451 83400242
10280 5 82325587 84254208 10324 5 82423451 83405797
10281 5 82325587 84314930 10325 5 82423451 83437132
10282 5 82325587 84340523 10326 . 5 82423451 83522252
10283 5 82325587 84516340 10327 5 82423451 83560095
10284 5 82325587 84706916 10328 5 82423451 83560204
10285 5 82325587 84799488 10329 5 82423451 83572400
10286 5 82325587 84801081 10330 5 82423451 83607661
10287 5 82325587 84824103 10131 5 82423451 83745342
10288 5 82325587 /14824203 10332 5 82423451 83861275
10289 5 82325587 84824816 10333 5 82423451 83861633
10290 5 82325587 84825422 10334 5 82423451 83865653
10291 5 82325587 84825763 10335 5 82423451 83865914
10292 5 82325587 84825942 10336 5 82423451 83865920
10293 5 82325587 84843411 10337 5 82423451 83868010
10294 5 82325587 84936441 10338 5 82423451 84019752
10295 5 82325587 84936493 10339 5 82423451 84065912
10296 5 12325587 84943705 10340 5 82423451 84086632
10297 5 8/325587 169454950 10341 5 82423451 84089603
10298 5 82325587 181522829 10342 5 82423451 84104814
10299 5 82325587 204759879 10343 5 82423451 84105175
10300 5 82325587 209874191 10344 5 82423451 84251635
10301 5 82423451 82427210 10345 5 82423451 84252180
10302 5 82423451 82431853 10346 5 82423451 84253033
10303 5 82423451 82446714 10347 5 82423451 84254208
10304 5 82423451 82446794 10348 5 82423451 84314930
10305 5 82423451 82551111 10349 5 82423451 84340523
10306 5 82423451 82552090 10350 5 82423451 84516340
227
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Bouadary2 Segment Chr
Boundaryl Boundary 2
10351 5 82423451 84706916 10395 5 82427780
83572400
10352 5 82423451 84799488 10396 5 82427780
83607661
10353 5 82423451 84801081 10397 5 82427780
83745342
10354 5 82423451 84824103 10398 5 82427780
83861275
10355 5 82423451 84824203 10399 5 82427780
83861633
10356 5 82423451 84824816 10400 5 824277110
83865653
10357 5 82423451 84825422 10401 5 82427780
83865914
10358 5 82423451 84825763 10402 5 82427780
83865920
10359 5 82423451- 84825942 10403 5 82427780
83868010
10360 5 82423451 84843411 10404 5 82427780
84019752
10361 5 82423451 84936441 10405 5 82427780
84065912
10362 5 82423451 84936493 10406 5 82427780
84086632
10363 5 82423451 84943705 10407 5 82427780
84089603
10364 5 82423451 169454950 10408 5 82427780
84104814
10365 5 82423451 181522829 10409 5 82427780
84105175
10366 5 82423451 204759879 10410 5 82427780
84251635
=
10367 5 82423451 209874191 10411 5 82427780
84252180
10368 5 82427780 82431853 10412 5 82427780
84253030
10369 5 82427780 82446714 10413 5 82427780
84254208
10370 5 82427780 82446794 10414 5 82427780
84314930
10371 5 82427780 82551111 10415 5 82427780
84340523
10372 5 82427780 82552090 10416 5 82427780
84516340
10373 5 82427780 82555641 10417 5 82427780
84706916
10374 5 82427780 82555670 10418 5 82427780
84799488
10375 5 82427780 82556511 10419 5 82427780
84801081
10376 5 82427780 82559047 10420 5 82427780
84824103
10377 5 82427780 82561535 10421 5 82427780
84824203
10378 5 82427780 82610100 10422 5 82427780
84824816
10379 5 82427780 82676822 10423 5 82427780
84825422
10380 5 82427780 82676901 10424 5 82427780
84825763
10381 5 82427780 82883691 10425 5 82427780
84825942
10382 5 82427780 82954942 10426 5 82427780
84843411
10383 5 82427780 82971688 10427 5 82427780
84936441
10384 5 82427780 83023965 10428 5 82427780
84936493
10385 5 82427780 83094205 10429 5 82427780
84943705
10386 5 82427780 83146355 10430 5 82427780
169454950
10387 5 82427780 83280630 10431 5 82427780
181522829
10388 5 82427780 83281412 10432 5 82427780
204759879
10389 5 82427780 83400242 10433 5 82427780
209874191
10390 5 82427780 83405797 10434 5 82443403
82446714
10391 5 82427780 83437132 10435 5 82443403
82446794
10392 5 82427780 83522252 10436 5 82443403
82551111
10393 5 82427780 83560095 10437 5 82443403
82552090
10394 5 82427780 83560204 10438 5 82443403
82555641
228
CA 02 9 3 95 8 0 2 0 16 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chnnnosmnal =
Segment Chr. Boundary1 Boundnry2 Segment Chr. Boundary 1
Boundary 2
10439 5 82443403 82555670 10483 5 82443403
84799488
13440 5 82443403 82556511 10484 5 82443403
84801081
10441 5 82443403 82559047 10485 5 82443403
84824103
10442 5 82443403 82561535 10486 5 82443403
84824203
10443 5 82443403 82610100 10487 5 82443403
84824818
10444 5 82443403 82676822 10488 5 82443403
84825422
10445 5 82443403 82676901 10489 5 82443403
84825763
10446 5 82443403 82883691 10490 5 82443403
84825942
10447 5 82443403 82954942 10491 5 82443403
84843411
10448 5 82443403 82971688 10492 5 82443403
84936441
10449 5 82443403 83023965 10493 5 82443403
84936493
10450 5 82443403 83094205 10494 5 82443403
84943705
10451 5 82443403 83146355 10495 5 82443403
169454950
10452 5 82443403 83280630 10496 5 82443403
181522829
10453 5 82443403 83281412 10497 5 82443403
204759879
10454 5 82443403 83400242 18498 5 82443403
209874191
10455 5 82443403 83405797 10499 5 82443815
82446714
10456 5 82443403 83437132 10500 5 82443815
82446794
10457 5 82443403 83522252 10501 5 82443815
82551111
10458 5 82443403 83560095 10502 5 82443815
82552090
10459 5 82443403 83560204 10503 5 82443815
82555641
10460 5 82443403 83572400 10504 5 82443815
82555670
10461 5 82443403 83607661 10505 5 82443815
82556511
10462 5 82443403 83745342 10506 5 82443815
82559047
10463 5 82443403 83861275 10507 5 82443815
82561535
10464 5 82443403 83861633 10508 5 82443815
82610100
10465 5 82443403 83865653 10509 5 82443815
82676822
10466 5 82443403 83865914 10510 5 82443815
82676901
10467 5 82443403 83865920 10511 5 82443815
82883691
10468 5 82443403 83868010 10512 5 82443815
82954942
10469 5 82443403 84019752 10513 5 82443815
82971688
10470 5 82443403 84065912 10514 5 82443815
83023965
10471 5 82443403 84086632 10515 5 82443815
83094205
10472 5 82443403 84089603 10516 5 82443815
83146355
10473 5 82443403 84104814 10517 5 82443815
83280630
10474 5 82443403 84105175 10518 5 82443815
83281412
10475 5 82443403 84251635 10519 5 82443815
83400242
10476 5 82443403 84252180 10520 5 82443815
83405797
10477 5 82443403 84253030 10521 5 82443815
83437132
10478 5 82443403 84254208 10522 5 82443815
83522252
10479 5 82443403 84314930 10523 5 82443815
83560095
10480 5 82443403 64340523 10524 5 82443815
83560204
10481 5 82443403 84516340 10525 5 82443815
83572400
10482 5 82443403 84706916 10526 5 82443815
83807861
229
CA 02939580 2016-08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (coned.)
Chumnosonud Chromosomal
Segment Chu Boundary1 13oundary2 Segment Chg. Boundary] '
Boundary2
10527 5 82443815 83745342 10571 5 82443856
82559047
10528 5 82443815 83861275 10572 5 82443856
82561535
10529 5 82443815 831161633 10573 5 82443856
82610100
10530 5 82443815 83865653 10574 5 82443856
82676822
10531 5 82443815 83865914 10575 5 82443856
82676901
10532 5 82443815 83865920 10576 5 82443856
82883691
10533 5 82443815 83868010 10577 5 82443856
82054942
10534 5 82443815 84019752 10578 9 82443856
82971688
10535 5 82443815 84065912 10579 5 82443856
83023965
10536 5 82443815 84086632 10580 5 82413856
83094205
10537 5 82143815 64089603 10581 5 82443856
83146355
10538 5 82443815 84104814 10582 5 82443856
83280630
10539 5 82443815 84105175 10583 5 82443856
83281412
10540 5 82443815 84251635 10584 5 82443856
83400242
10541 5 82443815 84252185 10585 5 82443856
83405797
10542 5 82443815 84253030 10586 5 82413856
83417132
10543 5 82443815 84254208 10587 5 82443856
83522252
10544 5 82443815 84314930 10588 5 82443856
83560095
10545 5 82443815 84340523 10589 5 82443856
83560204
10546 5 82441815 84516340 10590 5 82443856
83572400
10547 5 82443815 84706916 10591 5 82443856
83607661
10548 5 82443815 84799488 10592 5 82443856
83745342
10549 5 82443815 84801081 10593 5 82443856
83861275
10550 5 82443815 84824103 10594 5 82443856
83861633
10551 5 82413815 84824203 10595 5 82443856
83865653
10552 5 82443815 84824816 10596 5 82443856
83865914
10553 5 82443815 84825422 10597 5 82443856
83865920
10554 5 82443815 84825763 10598 5 82443856
83868010
10555 5 82443815 84825942 10599 5 82443856
84019752
10556 5 82443815 84843411 10600 5 82443856
84065912
10557 5 82443815 84936441 10601 5 82443856
84086632
10558 5 82443815 84936493 10602 5 82443856
84089603
10559 5 82443815 84943705 10603 5 82443856
84104814
10560 5 82443815 169454950 10604 5 82443856
84105175
10561 5 82443815 181522829 10605 5 82443856
01251635
10562 5 82443815 204759879 10606 5 82443856
84252180
10563 5 82443815 209874191 10607 5 82443856
84253030.
10564 5 82443856 82446714 10608 5 82443856
84254208
10565 5 82443856 82146794 10609 5 82443856
84314930
10566 5 82443856 82551111 10610 5 82443856
84340523
10567 5 82443856 82552090 10611 5 82443856
84516340
10568 5 82443856 82555641 10612 5 82443856
84706916
10569 5 82443856 82555670 10613 5 82443856
84799488
10570 5 82443856 82556511 10614 5 82443856
84801081
230
CA 02 9 3 95 8 0 2 0 16 ¨ 08 ¨ 11
WO 2015/127248 PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chummosmnal
Segment Chr. Boundaryl 13oun4ary2 Segment Chr. . Boundary]
Boundary2
10615 5 82443856 84824103 10659 5 82549227 83865914
10616 5 82443856 84824203 10660 5 82549227 83865920
10617 5 82443856 84824616 10661 5 82549227 83868010
10618 5 82443856 84025422 10662 5 82549227 84019752
10619 5 82443856 84825763 10663 5 82549227 84065912
. 10620 5 82443856 84625942 10664 5 82549227
84086632
10621 5 82443156 84843411 10665 5 82549227 84089603
10622 5 82443856 84936441 10666 5 82549227 84104814
10623 5 82443856 84936493 10667 5 82549227 84105175
10624 5 82443856 84943705 10668 5 82549227 84251635
10625 5 82443856 169454950 10669 5 82549227 84252180
10626 5 82443856 181522829 10670 5 82549227 84253030
10627 5 82443856 204759879 10671 5 82549227 84254208
10628 5 82443856 209874191 10672 5 82549227 84314930
10629 5 82549227 82551111 10673 5 82549227 84340523
10630 5 82549227 82552090 10674 5 82549227 _ 84516340
10631 5 82549227 82555641 10675 9 82549227 84706916
10632 5 82549227 82555670 10676 5 82549227 84799488
10633 5 82549227 82556511 10677 5 82549227 81801081
10634 5 82549227 82559047 10678 5 82549227 84824103
10635 5 82549227 82561535 10679 5 82549227 84824203
10636 5 82549227 82610100 10680 5 82549227 84824816
10637 5 82549227 82676822 10681 5 82549227 84825422
=
10638 5 82549227 82676901 10682 5 82549227 84825763
10639 5 82549227 82883691 10683 5 82549227 84825942
10640 5 82549227 82954942 10684 5 82549227 84843411
10641 5 82549227 .82971688 10685 5 82549227 84936441
10642 5 82549227 83023965 10686 5 82549227 84936493
10643 5 82549227 83094205 10687 5 82549227 84943705
10644 5 82549227 83146355 10688 5 82549227 169454950
10645 5 82549227 83280630 10689 5 82549227 181522829
10646 5 82549227 83281412 . 10690 5 82549227
204759879
10647 5 82549227 83400242 10691 5 82549227 209874191
10648 5 82549227 83405797 10692 5 82549246 '
82551111
10649 5 82549227 83437132 10693 5 82549246 82552090
10650 5 82549227 83522252 10694 5 82549246 82555641
10651 5 82549227 83560095 10695 5 82549246 82555670
.
10652 5 82549227 83560204 10696 5 82549246 82556511
10653 5 82549227 83572400 10697 5 82549246 82559047
10654 5 82549227 83607661 10698 5 82549246 82561535
10655 5 82549227 83745342 10699 5 82549246 82610100
10656 5 82549227 83861275 10700 5 82549246 82676822
10657 5 82549227 83861633 10701 5 82549246 82676901
10658 5 82549227 83865653 10702 5 82549246 82883691
231
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chnurmaanal
Segment COE Boundary1 Boundary2 Segment Cho. Boundary 1
Boundaty2
10703 5 82549246 82954942 10747 5 82549246
84843411
10704 5 82549246 82971688 10748 5 82549246
84936441
10705 5 82549246 83023965 10749 5 82549246
84936493
10706 5 82549246 83094205 10750 5 82549246
84943705
10707 5 82549246 83146355 10751 5 82549246
169454950
10708 5 82549246 83280630 10752 5 82549246
181522829
10709 5 82549246 83281412 10753 5 82549246
204759879
10710 5 82549246 83400242 10754 5 82549246
209874191
10711 5 82549246 83405797 10755 5 82549299
82551111
10712 5 82549246 83437132 10756 5 82549299
82552090
10713 5 82549246 83522252 10757 5 82549299
82555670
10714 5 82549246 83560095 10758 5 82549299
82556511
10715 5 82549246 83560204 10759 5 82549299
82559047
10716 5 82549246 83572400 10760 9 82549299
82561535
10717 5 82549246 83607661 10761 5 82549299
82610100
10718 5 82549246 83745342 10762 5 82549299
82676822
10719 5 82549246 83861275 10763 5 82549299
82676901
10720 5 82549246 83861633 10764 5 82549299
82883691
10721 5 82549246 83865653 10765 5 82549299
82954942
10722 5 82549246 83865914 10766 5 82549299
82971688
10723 5 82549246 83865920 10767 5 82549299
83023965
10724 5 82549246 83868010 10761 5 82549299
83094205
10725 5 82549246 84019752 10769 5 82549299
83146355
10726 5 82549246 84065912 10770 5 82549299
83280630
10727 5 82549246 84086632 10771 5 82549299
83281412
10728 5 82549246 84089603 10772 5 82549299
83400242
10729 5 82549246 84104814 10773 5 82549299
83405797
10730 5 82549246 84105175 10774 5 82549299
83437132
10731 5 82549246 84251635 10775 5 82549299
83522252
10732 5 82549246 84252180 10776 5 82549299
83560095
10733 5 82549246 84253030 10777 5 82549299
83560204
10734 5 82549246 84254208 10778 5 82549299
83572400
10735 5 82549246 84314930 10779 5 82549299
83607661
10736 5 82549246 84140523 10780 5 82549299
83745342
10737 5 82549246 84516340 10781 5 82549299
83861275
10738 5 82549246 84706916 10782 5 82549299
83861633
10739 5 82549246 84799488 10783 5 82549299
83865653
10740 5 82549246 84801081 10784 5 82549299
83865914
10741 5 82549246 84824103 10785 5 82549299
83865920
10742 5 82549246 84824203 10786 5 82549299
83868010
10743 5 82549246 84824816 10787 5 82549299
84019752
10744 5 82549246 81825422 10788 5 82549299
84065912
10745 5 82549246 841525763 10789 5 82549299
84086632
10746 5 82549246 84825942 10790 5 82549299
84089603
232
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Clue. Boundaryl Boandsay2 Segment Chr. Boundary 1
Paundary2
10791 5 82549299 84104814 10835 5 82554608
83522252
10792 9 62549299 84105175 10836 5 82554608
83560095
10793 5 62549299 84251635 10837 5 82554608
83560204
10794 5 82549299 84252180 10838 5 82554608
83572400
10795 5 82549299 84253030 10839 5 82554608
83607661
10796 5 82549299 84254208 10840 5 82554608
83745342
10797 5 82549299 64314910 10841 5 82554608
83861275
10798 5 82549299 84340523 10842 5 82554608
83861633
10799 5 82549299 84516340 10843 5 82554608
83865653
10800 5 82549299 84706916 10844 5 82554608
83865914
10801 5 82549299 84799488 10845 5 82554608
83865920
10802 5 82549299 84801081 10846 5 82554608
83868010
10803 5 62549299 84824103 10847 5 82554608
84019752
10804 5 82549299 84824203 10848 5 82554608
84065912
10805 5 82549299 84824816 10849 5 82554608
84086632
10806 5 82549299 84825422 10850 5 82554608
84089603
10807 5 82549299 84825763 10851 5 12554608
84104814
10808 5 82549299 84825942 10852 5 82554608
84105175
10809 5 82549299 84843411 10853 5 82554608
84251635
10810 5 82549299 84936441 10854 5 82554608
84252180
10811 5 82549299 64936493 10855 5 82554608
84253030
10/112 5 82549299 84943705 10856 5 82554600
84254208
10813 5 82549299 169454950 10857 5 82554608
84314930
10814 5 82549299 181522829 10858 5 82554608
84340523
10815 5 82549299 204759879 10859 5 82554608
84516340
10816 5 82549299 209874191 10860 5 82554608
84706916
10817 5 82554608 82555670 10861 5 82554608
84799488
10818 5 82554608 82556511 10862 5 82554608
84801081
10819 5 82554608 82559047 10863 . 5 82554608
84824103
10820 5 82554608 82561535 10864 5 82554608
84824203
10821 5 82554608 82610100 10665 5 82554608
84824816
10822 5 82554608 82676822 10866 5 82554608
84825422
10823 5 82554608 82676901 10867 5 82554608
84825763
10824 5 82554608 82883691 10868 5 82554608
84825942
10825 5 82554608 82954942 10869 5 82554608
84843411
10826 5 82554608 82971688 10870 5 82554608
84936411
10827 5 82554608 83023965 10871 5 82554608
84936493
10828 5 82554608 83094205 10872 5 82554608
84943705
10829 5 82554608 83146355 10873 - 5 82554608
169454950
10830 5 82554608 83280630 10874 5 82554608
181522829
10831 5 82554608 83281412 10875 5 82554608
204759879
10832 5 82554608 83400242 10876 5 82554608
209874191
10833 5 82554608 83405797 10877 5 82554971
82555670
10834 5 82554608 83437132 10878 5 82554971
82556511
233
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chr. BoundaryI Boundary2 Segment CUL Bounthary1 Boundary2
10879 5 82554971 82559047 10923 5 82554971
84824103
10880 5 82554971 82561535 10924 5 82554971
84824203
10881 5 82554971 82610100 10925 5 82554971
84824816
10882 5 82554971 82676822 10926 5 82554971
84825422
10883 5 82554971 82676901 10927 5 82554971
84825763
10884 5 82554971 82883691 10928 5 82554971
84825942
10885 5 82554971 82954942 10929 5 82554971
84843411
10886 5 82554971 82971688 10930 5 82554971
84936441
10887 5 82554971 83023965 10931 5 82554971
84936493
10888 5 82554971 83094205 10932 5 82554971
84943705
10889 5 82554971 83146355 10933 5 82554971
169454950
10890 5 82554971 83280630 10934 5 82554971
181522829
10891 5 82554971 83281412 10935 5 82554971
204759879
10892 5 82554971 83400242 10936 5 82554971
209874191
10893 5 82554971 83405797 10937 5 82556313
82556511
10894 5 82554971 83437132 10938 5 82556313
82559047
10895 5 82554971 83522252 10939 5 82556313
82561535
10896 5 82554971 83560095 10940 5 82556313
82610100
10897 5 82554971 83560204 10941 5 82556313
82676822
10898 5 82554971 83572400 10942 5 82556313
82676901
10899 5 82554971 83607661 10943 5 82556313
82883691
10900 5 82554971 83745342 10944 5 82556313
82954942
10901 5 82554971 83861275 10945 5 82556313
82971688
10902 5 82554971 83861633 10946 5 82556313
83023965
10903 5 82554971 83065653 10947 5 82556313
83094205
10904 5 82554971 83865914 10948 5 82556313
83146355
10905 5 82554971 83865920 10949 5 82556313
83280630
10906 5 82554971 83868010 10950 5 82556313
83281412
10907 5 82554971 84019752 10951 5 82556313
83400242
10908 5 82554971 84065912 10952 5 82556313
83405797
10909 5 82554971 84086632 10953 5 82556313
83437132
. 10910 5 82554971 84089603 10954 5 82556313
83522252
10911 5 82554971 84104814 10955 5 82556313
83560095
10912 5 82554971 84105175 10956 5 82556313
83560204
10913 5 82554971 84251635 10957 5 82556313
83572400
10914 5 82554971 84252180 10958 5 82556313
83607661
10915 5 82554971 84253030 10959 5 82556313
83745342
10916 5 82554971 84254208 10960 5 82556313
83861275
10917 5 82554971 84314930 10961 5 82556313
83861633
10918 5 82554971 84340523 10962 5 82556313
83865653
10919 5 82554971 84516340 10963 5 82556313
83865914
10920 5 82554971 84706916 10904 5 82556313
83865920
10921 5 82554971 84799488 10965 5 82556313
83868010
10922 5 82554971 84801081 10966 5 82556313
84019752
234
CA 0 2 9 3 95 8 0 2 0 1 6 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chronmsonml
Segment Cht Boundmyl Boundary2 Segment Om Boundary 1
8oundary2
10967 5 82556313 84065912 11011 5 82556337 83405797
10968 5 82556313 84086632 11012 5 82556337 83437132
10969 5 82556313 84089603 11013 5 82556337 83522252
10970 5 82556313 84104814 11014 5 82556337 83560095
10971 5 82556313 84105175 11015 5 82556337 83560204
10972 5 82556313 84251635 11016 5 82556337 83572400 .
10973 5 82556313 04252180 11017 5 82556337 83607661
10974 5 82556313 84253030 11018 5 82556337 83745342
10975 5 82556313 84254208 11019 5 82556337 83861275
10976 5 82556313 84314930 11020 5 82556337 83861613
10977 5 82556313 84340523 11021 5 82556337 83865653
10978 5 82556313 84516340 11022 5 82556337 83865914
10979 5 82556313 84706916 11023 5 82556337 83865920
10980 5 82556313 84799488 11024 5 02556337 83868010
10981 5 82556313 848010111 11025 5 82556337 84019752
10982 5 82556313 84824103 11026 5 82556337 84065912
10983 5 82556313 84824203 11027 5 82556337 84086632
10984 5 82556313 01824816 11028 5 82556337 84089603
10985 5 82556313 84825422 11029 5 82556337 84104014
10986 5 82556313 84825763 11030 5 82556337 84105175
10987 5 82556313 84825942 11031 5 82556337 84251635
10988 5 82556313 84843411 11032 5 82556337 84252180
10989 5 82556313 84936441 11033 5 82556337 84253030
10990 5 82556313 84936493 11034 5 82556337 84254208
10991 5 82556313 84943705 11035 5 82556337 84314930
10992 5 82556313 169454950 11036 5 82556337 84340523
10993 5 82556313 181522829 11037 5 82556337 84516340
10994 5 82556313 204759879 11038 5 82556337 84706916
10995 5 82556313 209874191 11039 5 82556337 84799488
10996 5 82556337 82556511 11040 5 82556337 84801081
10997 5 82556337 82559047 11041 5 82556337 84824103
10998 5 82556337 82561535 11042 5 82556337 84824201
10999 5 82556337 82610100 11043 5 82556337 84874816
11000 5 82556337 82676822 11044 5 82556337 84825422
11001 5 82556337 82676901 11045 5 82556337 84825763
11002 5 82556337 82883691 11046 5 82556337 84825942
11003 5 82556337 82954942 11047 5 82556337 84843411
11004 5 82556337 82971688 11048 5 82556337 84936441
11005 5 82556337 83023965 11049 5 82556337 84936493
11006 5 82556337 83094205 11050 5 82556337 84943705
11007 5 82556337 83146355 11051 5 82556337 169454950
11008 5 82556337 83280630 11052 5 82556337 181522829
11009 5 82556337 83281412 11053 5 82556337 204759879
11010 5 82556337 83400242 11054 5 82556337 209874191
235
CA 02 9 3 958 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chrmnosmng
Segment Chr. Bounduly1 Boundmy2 Segment Om Boundary] 14oundary2
11055 5 82556511 82609175 11099 5 82556511
84824203
11056 5 82556511 82610100 11100 5 82556511
84824816
11057 5 82556511 82676822 11101 5 82556511
84825422
11058 5 82556511 82676901 11182 5 82556511
84825763
11059 5 82556511 82883691 11103 5 82556511
84825942
11060 5 82556511 82954942 11104 5 82556511
84843411
11061 5 82556511 82971688 11105 5 82556511
84936441
11062 5 82556511 83023965 11106 5 82556511
84936493
11863 5 82556511 83094205 11107 5 82556511
84943705
11064 5 82556511 83146355 11108 5 82556511
169454950
11065 5 82556511 83280630 11109 5 82556511
181522829
11866 5 82556511 83281412 11110 5 82556511
204759879
11067 5 82556511 83400242 11111 5 82556511
209874191
11068 5 82556511 83405797 11112 5 82609175
82610100
11069 5 82556511 83437132 11113 5 82609175
82676822
11070 5 82556511 83522252 11114 5 82609175
82676901
11071 5 82556511 83560095 11115 5 82609175
82883691
11072 5 82556511 83560204 11116 5 82609175
82954942
11073 5 82556511 83572400 11117 5 82609175
82971688
11074 5 82556511 83607661 11118 5 82609175
83023965
11075 5 82556511 83745342 11119 5 82609175
83094205
11076 5 82556511 83861275 11120 5 82609175
83146355
11077 5 82556511 83861633 11121 5 82609175
83280630
11078 5 82556511 83865653 11122 5 82609175
83281412
11079 5 82556511 83865914 11123 9 82609175
83400242
11080 5 82556511 83865920 11124 5 82609175
83405797
11081 5 82556511 83868010 11125 5 82609175
83437132
11082 5 82556511 84019752 11126 5 82609175
83522252
11083 5 82556511 84065912 11127 5 82609175
83560095
11084 5 82556511 84086632 11128 5 82609175
83560204
11085 5 82556511 84089603 11129 5 82609175
83572400
11086 5 82556511 84104814 11130 5 82609175
83607661
11087 5 82556511 84105175 11131 5 82609175
81745342
11088 5 82556511 84251635 11132 5 82609175
83861275
11089 5 82556511 84252180 11133 5 82609175
83861633
11090 5 82556511 84253030 11134 5 82609175
83865653
11091 5 82556511 84254208 11135 5 82609175
83865914
11092 5 82556511 84314930 11136 5 82609175
83865920
11093 5 82556511 84340523 11137 5 82609175
83868010
11094 5 82556511 84516340 11138 5 82609175
84019752
11095 5 82556511 84706916 11139 5 82609175
84065912
11096 5 82556511 84799488 11140 5 82609175
84086632
11097 5 82556511 84/101081 11141 5 82609175
84089603
11098 5 82556511 84824103 11142 5 82609175
84104814
236
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Clumnosonud
Segment Chtt Boundary 1 Boundary2 Segment Chn Boundary1
Daundary2
11143 5 82609175 84105175 11187 5 82675654
83861275
11144 5 82609175 84251635 11188 5 82675654
83861633
11145 5 82609175 84252180 11189 5 82675654
83865653
11146 5 82609175 84253030 11190 5 82675654
83865914
11147 5 82609175 84254208 11191 5 82675654
83865920
11148 5 82609175 84314930 11192 5 82675654
83868010
11149 5 82609175 84340523 11193 5 82675654
84019752
11150 5 82609175 84516340 11194 5 82675654
84065912
11151 5 82609175 84706916 11195 5 82675654
84086632
11152 5 82609175 84799488 11196 5 82675654
84089603
11153 5 82609175 84801081 11197 5 82675654
84104814
11154 5 82609175 84824103 11198 5 82675654
84105175
11155 5 82609175 84824203 11199 5 82675654
84251635
11156 5 82609175 84824816 11200 5 82675654
84252180
11157 5 82609175 84825422 11201 5 82675654
84253030
11158 5 82609175 84825763 11202 5 82675654
84254208
11159 5 82609175 84825942 11203 5 82675654
84314930
11160 5 82609175 84843411 11204 5 82675654
84340523
11161 5 82609175 84936441 11205 5 82675654
84516340
11162 5 82609175 84936493 11206 5 82675654
84706916
11163 5 82609175 84943705 11207 5 82675654
84799488
11164 5 82609175 169454950 11208 5 82675654
84801081
11165 5 82609175 181522829 11209 5 82675654
84824103
11166 5 82609175 204759879 11210 5 82675654
84824203
11167 5 82609175 209874191 11211 5 82675654
84824816
11168 5 82675654 82676822 11212 5 82675654
84825422
11169 5 82675654 82676901 11213 5 82675654
84825763
11170 5 82675654 82883691 11214 5 87675654
84825942
11171 5 82675654 82954942 11215 5 82675654
64843411
11172 5 82675654 82971688 11216 5 82675654
84936441
11173 5 82675654 83023965 11217 9 82675654
84936493
11174 5 82675654 83094205 11218 5 82675654
84943705
11175 5 82675654 83146355 11219 5 82675654
169454950
11176 5 82675654 83280630 11220 5 82675654
181522829
11177 5 82675654 83281412 11221 5 82675654
204759879
11178 5 82675654 83400242 11222 5 82675654
209874191
11179 5 82675654 83405797 11223 5 82675825
82676822
11180 5 82675654 83437132 11224 5 82675825
82676901
11181 5 82675654 83522252 11225 5 82675825
82883691
11182 5 82675654 83560095 11226 5 82675825
82954942
11183 5 82675654 83560204 11227 5 82675825
82971688
11184 5 82675654 83572400 11228 5 82675825
83023965
11185 5 82675654 83607661 11229 5 82675825
83094205
11186 5 82675654 83745342 11230 5 82675825
83146355
237
CA 0 2 9 3 95 8 0 2 0 1 6 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chnnnosonml
Segment Chr. Boundaryl Boundaly2 Segment Cho. Boundary!
Boundary 2
11231 5 82675825 83280630 11275 5 82675825
181522829
11232 5 82675825 83281412 11276 5 82675825
204759879
11233 5 82675825 83400242 11277 5 82675825
209874191
11234 5 82675825 83405797 11278 5 82882273
82883691
11235 5 82675825 83437132 11279 5 82882273
82954942
._
11236 5 82675825 83522252 11280 5 82882273
82971688
11237 5 82675825 83560095 11281 5 82882273
83023965
11238 5 82675825 83560204 11282 5 82882273
83094205
11239 5 82675825 83572400 11283 5 82882273
83146355
11240 5 82675825 83607661 ' 11284 5 82882273 83280630
11241 5 82675825 83745342 11285 5 82882273
83281412
11242 5 82675825 83861275 11286 5 82882273
83400242
11243 5 82675825 83861633 11287 5 82882273
83405797
11244 5 82675825 83865653 11288 5 82882273
83437132
11245 5 82675825 83865914 11289 5 82882273
83522252
11246 5 82675825 83865920 11290 5 82882273
83560095
11247 5 82675825 83868010 11291 5 82882273
83560204
11248 5 82675825 84019752 11292 5 82882273
83572400
11249 5 82675825 84065912 11293 5 82882273
83607661
11250 5 82675825 84086632 11294 5 82882273
83745342
11251 5 82675825 84089603 11295 5 82882273
83861275
11252 5 82675825 84104814 11296 5 82882273
83861633
11253 5 82675825 84105175 11297 5 82882273
83865653
11254 5 82675825 84251635 11298 5 82882273
83865914
11255 5 82675825 84252180 11299 5 82882273
83865920
11256 5 82675825 84253030 11300 5 82882273
83868010
11257 5 82675825 84254208 11301 5 82882273
84019752
11258 5 82675825 84314930 11302 5 82882273
84065912
11259 5 82675825 84340523 11303 5 82882273
84086632
11260 5 82675825 84516340 11304 5 82882273
84089603
11261 5 82675825 84706916 11305 5 82882273
84104814
11262 5 82675825 84799488 11306 5 82882273
84105175
11263 5 82675825 84801081 11307 5 82882273
84251635
11264 5 82675825 84824103 11308 5 82882273
84252180
11265 5 82675825 84824203 11309 5 82832273
84253030
11266 5 82675825 84824816 11310 5 82882273
84254208
11267 5 82675825 84825422 11311 5 82882273
84314930
11268 5 82675825 84825763 11312 5 82882273
84140523
11269 5 82675825 84825942 11313 5 82882273
84516340
11270 5 82675825 84843411 11314 5 82882273
84706916
11271 5 82675825 84936441 11315 5 82882273
84799488
11272 5 82675825 84936493 11316 5 82882273
84801081
11273 5 82675825 84943705 11317 5 82882273
84824103
11274 5 82675825 169454950 11318 5 82862273
84824203
238
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd)
Chromosomal Chnmmosmnd
Segment Chn Boundary 1 Boundary 2 Segment Chr, Boundmyl
Boundary2
11319 5 82882273 84824816 11363 5 82953053 84314910
11320 5 62882273 84825422 11364 5 82951053 84340523
11321 5 82882273 84825763 11365 5 82953053 84516340
11322 5 82882273 84825942 11366 5 82953053 84706916
11323 5 82882273 84843411 11367 5 82953053 84799488
11324 5 82882273 84936441 11368 5 82953053 84801081
11325 5 82882273 84936493 11369 5 82953053 84824103
11326 5 82882273 84943705 11370 5 82953053 84824203
11327 5 82882273 169454950 11371 5 82953053 84824816
11328 5 82882273 181522829 11372 5 82953053 84825422
11329 5 82882273 204759879 11373 5 82913053 84825763
11330 5 82882273 209874191 11374 5 82953053 84825942
11331 5 82953053 82954942 11375 5 82953013 84843411
11332 5 82953053 82971688 11376 5 82953053 84936441
11333 5 82913053 83023965 11377 5 82953053 84936493
11334 5 82953053 81094205 11378 5 82953053 84943705
11335 5 82953053 83146355 11379 5 82953053 169454950
11336 5 82953053 83280630 11380 5 82953053 181522829
11337 5 82953053 83281412 11381 5 82953053 204759879
11338 5 82953053 83400242 11382 5 82953053 209874191
11339 5 82953053 83405797 11383 5 82971168 82971688
11340 5 82953053 83437132 11184 5 82971168 83023965
11341 5 82953053 83522252 11385 5 82971168 83094205
11342 5 82953053 83560095 11386 5 82971168 83146355
11343 5 82953053 83560204 11387 5 82971168 83280630
11344 5 82953053 83572400 11388 5 82971168 83281412
11345 5 82953053 83607661 11389 5 82971168 83400242
11346 5 82953053 83745342 11390 5 82971168 83405797
11347 5 82953053 83861275 11391 5 82971168 83437132
11348 5 82953053 83861633 11392 5 82971168 83522252
11349 5 82953053 83865653 11393 5 82971168 83560095
11350 5 82953053 83865914 11394 5 82971168 83560204
11351 5 82953053 83865920 11395 5 82971168 83572400
11352 5 82953053 83868010 11396 5 82971168 83607661
11353 5 82953053 84019752 11397 5 82971168 83745342
11354 5 82953053 84065912 11398 5 82971168 83861275
11355 5 82953053 84086632 11399 5 82971168 83861633
11356 5 82953053 84089603 11400 5 82971168 83865653
11357 5 82953053 84104814 11401 5 82971168 83865914
11358 5 82951053 84105175 11402 5 82971168 83865920
11359 5 82953053 84251635 11403 5 82971168 83868010
11360 5 82953053 84252180 11404 5 82971168 84019752
11361 5 82953013 84253030 11405 5 82971168 84065912
11362 5 82953053 84254208 11406 5 82971168 84086632
239
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248 PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segamnt Chr. Boundary] Boundary 2 Segment Chr. Boundaryl
Boundary 2
11407 5 82971168 84089603 11451 5 83023500 83865914
11408 5 82971168 84104814 11452 5 83023500 83865920
11409 5 82971168 84105175 11453 5 83023500 83868010
11410 5 82971168 84251635 11454 5 83023500 84019752
11411 5 82971168 84252180 11455 5 83023500 84065912
11412 5 92971168 84253030 11456 5 83020500 84086632
11413 5 82971168 84254208 11457 5 83023500 84089603
11414 5 82971168 84314930 11458 5 83023500 84104814
11415 5 82971168 84340523 11459 5 83023500 84105175
11416 5 82971168 84516340 11460 5 83023500 84251635
11417 5 82971168 84706916 11461 5 83023500 84252180
11418 5 82971168 84799488 11462 5 83023500 84253030
11419 5 82971168 84801081 11463 5 83023500 84254208
11420 5 82971168 84624103 11464 5 83023500 84014930
11421 5 82971168 84824203 11465 5 83023500 84340523
11422 5 82971168 84824816 11466 5 83023500 84516340
11423 5 82971168 84825422 11467 5 83023500 84706916
11424 5 82971168 84825763 11468 5 83023500
84799488
11425 5 82971168 84825942 11469 5 83023530 84801081
11426 5 82971168 84843411 11470 5 83023500 84824103
11427 5 82971168 84936441 11471 5 83023500 84824203
11428 5 82971168 84936493 11472 5 83023500 84824816
11429 5 82971168 84943705 11473 5 83023500 84825422
11430 5 82971168 169454950 11474 5 83023500 84825763
11431 5 82971168 181522829 11475 5 83023500 84825942
11432 5 82971168 204759879 11476 5 83023500 84843411
11433 5 82971168 209874191 11477 5 83023500 84936441
11434 5 83023500 83023965 11478 5 83023500 84936493
11435 5 83023500 83094205 11479 5 83023500 84943705
11436 5 83023500 83146355 11480 5 83023500 169454950
11437 5 83023500 83280630 11481 5 83023500 181522829
11438 5 83023500 83281412 11482 5 83023500 204759879
11439 5 83023500 83400242 11483 5 83023500 209874191
11440 5 83023500 83405797 11484 5 83093332 83094205
11441 5 83023500 83437132 11485 5 83093332 83146355
11442 5 83023500 83522252 11486 5 83093332 83280630
11443 5 83023500 83560095 11487 5 83093332 83281412
11444 5 83023500 83560204 11488 5 83093332 83400242
11445 5 83023500 83572400 11489 5 83093332 83405797
11446 5 83023560 83607661 11490 5 83493332 83437132
11447 5 83023500 83745342 11491 5 83093332 83522252
11448 5 83023500 83861275 11492 5 83093332 83560095
11449 5 83023500 83861633 11493 5 83093332 83560204
11450 5 83023500 83865653 11494 5 83093332 83572400
240
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'cL)
CluornosmnW Chromosomal
Segment Chi. Boundaryl Boundary2 Segment Chi. Boundary1 Boundaly2
11495 5 83093332 83607661 11539 5 83145879 83522252
11496 5 83093332 83745342 11540 5 83145879 83560095
11497 5 83093332 83861275 11541 5 83145879 83560204
11498 5 83093332 83861633 11542 5 83145879 83572400
11499 5 83093332 83865653 11543 5 83145879 83607661
11500 5 83093332 83865914 11544 5 83145879 83745342
11501 5 83093332 83865920 11545 5 83145879 83861275
11502 5 83093332 83868010 11546 5 83145879 83861633
11503 5 83093332 84019752 11547 5 83145879 83865653
11504 5 83093332 84065912 11548 5 83145879 83865914
11505 5 83093332 84086632 11549 5 83145879 83865920
11506 5 83093332 84089603 11550 5 83145879 83868010
11507 5 83093332 84104814 11551 5 83145879 84019752
11508 5 83093332 84105175 11552 5 83145879 84065912
11509 5 83093332 84251635 11553 5 83145879 84086632
11510 5 83093332 84252180 11554 5 83145879 84089603
11511 5 83093332 84253030 11555 5 83145879 84104814
11512 5 83093332 84254208 11556 5 83145879 84105175
11513 5 83093332 84314930 11557 5 83145879 84251635
11514 5 83093332 84340523 11558 5 83145879 84252180
11515 5 83093332 84516340 11559 5 83145879 84253030
11516 5 83093332 84706916 11560 5 83145879 84254208
11517 5 83093332 84799488 11561 5 83145879 84314930
11518 5 83093332 84801081 11562 5 83145879 84340523
11519 5 83093332 84824103 11563 5 83145879 84516340
11520 5 83093332 84824203 11564 5 83145879 84706916
11521 5 83093332 84824816 11565 5 83145879 84799488
11522 5 83093332 84825422 11566 5 83145879 84801081
11523 5 83093332 84825763 11567 5 83145879 84824103
11524 5 83093332 84825942 11568 5 83145879 84824203
11525 5 83093332 84843411 11569 5 83145879 84824816
11526 5 83093332 84936441 11570 5 83145879 84821d27
11527 5 83093332 84936493 11571 5 83145879 84825763
11528 5 83093332 84943705 11572 5 83145879 84825942
11529 5 83093332 169454950 11573 5 83145879 84843411
11530 5 83093332 181522829 11574 5 83145879 84936441
11531 5 83093332 204759879 11575 5 83145879 84936493
11532 5 83093332 209874191 11576 5 83145879 84943705
11533 5 83145879 83146355 11577 5 83145879 169454950
11534 5 83145879 83280630 11578 5 83145879 181522829
11535 5 13145879 83281412 11579 5 83145879 204759879
11536 5 83145879 83400242 11580 5 83145879 209874191
11537 5 83145879 83405797 11581 5 83277783 83280630
11538 5 83145879 83437132 11582 5 83277783 83281412
241
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chronumomal Chromosomal
Segment Oa Boundmyl Boundary2 Segment Cht Boundaryl Boundary2
11583 5 83277783 83400242 11627 5 83277783 209874191
11584 5 83277783 83405797 11628 5 83277785 13280630
11585 5 83277783 83437132 11629 5 83277785 83281412
11586 5 83277783 83522252 11630 5 83277785 83400242
11587 5 83277783 83560595 11631 5 83277785 83405797
11588 5 81277783 83560204 11632 5 83277785 83437132
11589 5 83277783 83572400 11633 5 83277785 83522252
11590 5 83277783 83607661 11634 5 83277785 83560095
11591 5 83277783 83745342 11635 5 83277785 83560204
11592 5 83277783 83861275 11636 5 83277785 83572400
11593 5 83277783 83861633 11637 5 83277785 83607661
11594 5 83277783 83865653 11638 5 83277785 83745342
11595 5 83277783 83865914 11639 5 83277785 83861275
11596 5 83277783 83865920 11640 5 83277785 83861633
11597 5 83277783 83868010 11641 5 83277785 83865653
11598 5 83277783 84019752 11642 5 83277785 83865914
11599 5 83277783 84065912 11643 5 83277785 83865920
11600 5 83277783 84086632 11644 5 83277785 83868010
11601 5 83277783 84069603 11645 5 83277785 84019752
11602 5 83277783 84104814 11646 5 83277785 84065912
11603 5 83277783 84105175 11647 5 83277785 84086632
11604 5 83277783 84251635 11648 5 83277785 84089603
11605 5 83277783 84252180 11649 5 83277785 84104814
11606 5 83277783 84253030 11650 5 83277785 84105175
11607 5 83277783 84254208 11651 5 83277785 84251635
11608 5 83277783 84314930 11652 5 83277785 84252180
11609 5 83277783 84340523 11653 5 83277785 94253035)
11610 5 83277783 84516340 11654 5 83277785 84254208
11611 5 83277783 84706916 11655 5 83277785 84314930
11612 5 83277783 84799488 11656 5 83277785 84340523
11613 5 83277783 84801081 11657 5 83277785 84516340
11614 5 83277783 84824103 11658 5 83277785 84706916
11615 5 83277783 84824203 11659 5 83277785 84799488
11616 5 83277783 84824816 11660 5 83277785 84801081
11617 5 83277783 84825422 11661 5 83277785 84824103
11618 5 83277783 84825763 11662 5 83277785 84824203
11619 5 83277783 84825942 11663 5 83277785 84824816
11620 5 83277783 84843411 11664 5 83277785 84825422
11621 5 83277783 84936441 11665 5 83277785 84825763
11622 5 83277783 84936493 11666 5 83277785 84825942
11623 5 83277783 84943705 11667 5 83277785 84843411
11624 5 83277783 169454950 11668 5 83277785 84936441
11625 5 83277783 181522829 11669 5 83277785 84936493
11626 5 83277783 204759879 11670 5 83277785 84943705
242
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chrmnoscand
Segment Chr. Boundary 1 Boundary2 Segnent Cho. Boundanyl
Boundary2
11671 5 83277785 169454950 11715 5 83279034 84936441
11672 5 83277785 181522829 11716 5 83279034 84936493
11673 5 83277785 204759879 11717 5 83279034 84943705
11674 5 83277785 209874191 11718 5 83279034 169454950
11675 5 83279034 83280630 11719 5 83279034 181522829
11676 5 83279034 83281412 11720 5 83279034 204759879
11677 5 83279034 83400242 11721 5 83279034 209874191
11678 5 83279034 83405797 11722 5 81397014 83400242
11679 5 83279034 83437132 11723 5 83397014 83405797
11680 5 83279034 83522252 11724 5 83397014 83437132
11681 5 83279034 83560095 11725 5 83397014 83522252
11682 5 83279034 83560204 11726 5 83397014 83560095
11683 5 83279034 83572400 11727 5 83397114 83560204
11684 5 83279034 83607661 11728 5 83397014 83572400
11605 5 83279034 83745342 11729 5 83397014 83607661
11686 5 83279034 83861275 11730 5 83397014 83745342
11687 5 83279034 83861633 11731 5 83397014 83861275
11688 5 83279034 83865653 11732 5 83397014 83861633
11689 5 83279034 83865914 11733 5 83397014 83865653
11690 5 83279014 83865920 11734 5 83397014 83865914
11691 5 83279034 83868010 11715 5 83397014 83865920
11692 5 83279034 84019752 11736 5 83397014 83868010
11693 5 83279034 84065912 11737 5 83397014 84019752
11694 5 83279014 84086632 11738 5 83397014 84065912
11695 5 83279034 84089603 11739 5 83397014 84086632
11696 5 83279034 84104814 11740 5 83397014 84009603
11697 5 83279034 84105175 11741 5 83397014 84104814
11698 5 83279034 84251635 11742 5 83397014 84105175
11699 5 83279034 84252180 11743 5 83397014 84251635
11700 5 83279034 84253030 11744 5 83397014 84252180
11701 5 83279034 84254208 11745 5 83397014 84253030
11702 5 83279034 84314930 11746 5 83397014 84254208
11703 5 83279034 84340523 11747 5 83397014 84314930
11704 5 83279034 84516340 11748 5 13397014 84340523
11705 5 83279034 84706916 11749 5 83397014 84516340
11706 5 83279034 84799488 11750 5 83397014 84706916
11707 5 83279034 84801081 11751 5 83397014 84799488
11708 5 83279034 84874103 11752 5 83397014 84801081
11709 5 83279034 84824203 11753 5 83397014 84824103
11710 5 83279034 84824816 11754 5 83397014 84824203
11711 5 83279034 84825422 11755 5 83397014 84824816
11712 5 83279034 84825763 11756 5 83397014 84825422
11713 5 83279034 84825942 11757 5 83397014 84825763
11714 5 83279034 84843411 11758 5 83397014 84825942
243
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Channosorual
Seguleat Cho. Boundary1 Boundary 2 Segment Ch,
Boundary] Boundary2
11759 5 83397014 84843411 11803 5 83402967 84843411
11760 5 83397014 84936441 11804 5 83402967 '
84936441
11761 5 83397014 84936493 11805 5 83402967 84936493
11762 5 83397014 84943705 11806 5 83402967 84943705
11763 5 83397014 169454950 11807 5 83402967 169454950
11764 5 83397014 181522829 11808 5 83402967 181522829
11765 5 83397014 204759879 11809 5 83402967 204759879
11766 5 83397014 209874191 11810 5 83402967 209874191
11767 5 83402967 83405797 11811 5 83435480 83437132
11768 5 83402967 83437132 11812 5 83435480 83522252
11769 5 83402967 83522252 11813 5 83435480 83560095
11770 5 83402967 83560095 11814 5 83435480 83560204
11771 5 83402967 83560204 11815 5 83435480 83572400
11772 5 83402967 83572400 11816 5 81435480 83607661
11773 5 83402967 83607661 11817 5 83435480 83745342
11774 5 83402967 83745342 11818 5 83435480 83861275
11775 5 83482967 83861275 11819 5 83435480 83861633
11776 5 83402967 83861633 11820 5 83435480 83865653
11777 5 83402967 83865653 11821 5 83435480 83865914
11778 5 83402967 83865914 11822 5 83435480 83865920
11779 5 83402967 83865920 11823 5 83435480 83868010
11760 5 83402967 83868010 11824 5 83435480 84019752
11781 5 83402967 84019752 11825 5 83435480 84065912
11782 5 83402967 84065912 11826 5 83435480 84086632
11783 5 83402967 84086632 11827 5 83435480 84089603
11784 5 83402967 8408960.3 11828 5 83435480 84104814
11785 5 83402967 84104814 11829 5 83435480 84105175
.
11786 5 83402967 84105175 11830 5 83435480 84251635
11787 5 81402967 84251635 11831 5 83435480 84252180
11788 5 83402967 84252180 11832 5 83435480 84253030
11789 5 83402967 84253030 11833 0 83435480 84254208
11790 5 83402967 84254208 11634 5 83435480 84314930
11791 5 83402967 84314930 11835 5 83435480 84340523
11792 5 83402467 84340523 11836 5 83435480 84516340
11793 9 63402967 84516340 11837 5 83435480 84706916
11794 5 83402967 84706916 11838 5 83435480 84799488
11795 5 83402967 84799488 11839 5 83435480 84801081
11796 5 83402967 84801081 11840 5 83435480 84824103
11797 5 83402967 84824103 11841 5 83435480 84824203
11798 5 83402967 84024203 11842 5 83435480 84824816
11799 5 83402967 84824816 11843 5 83435480 84825422
11800 5 83402967 84825422 11844 5 83435480 84825763
11801 5 83402967 84825763 11845 5 83435480 84825942
11802 5 83402967 84825942 11846 5 83435480 84843411
244
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (coned.)
ChrornomnnM Chromosomal
Segment Chr. Boundary 1 Boundary2 Segment Chi. Boundary
1 Boundary2
11847 5 83435480 84936441 11891 5 83521923
84943705
11848 5 83435480 84936493 11892 5 83521923
169454950
11849 5 83435480 84943705 11893 5 83521923
181522829
11850 5 83435480 169454950 11894 5 83521923
204759879
11851 5 83435480 181522829 11895 5 83521923
209874191
11852 5 83435480 204759879 11896 5 83557023
83560095
11853 5 83435480 209874191 11897 5 83557023
83560204
11854 5 83521923 83522252 11898 5 83557023
83572400
11855 5 83521923 83560095 11899 5 83557023
83607661
11856 5 83521923 83560204 11900 5 83557023
83745342
11857 5 83521923 83572400 11901 5 83557023
83861275
11858 5 83521923 83607661 11902 5 83557023
83861633
11859 5 83521923 83745342 11903 5 83557023
83865653
11860 5 83521923 83861275 11904 5 83557023
83865914
11861 5 83521923 83861633 11905 5 83557023
83865920
11862 5 83521923 83865653 11906 9 83557023
83868010
11863 5 83521923 03865914 11907 5 83557023
84019752
11864 5 83521923 83865920 11908 5 83557023
84065912
11865 5 83521923 83868010 11909 5 83557023
84086632
11866 5 83521923 84019752 11910 5 83557023
84089603
11867 5 83521923 84065912 11911 5 83557023
84104814
11868 5 83521923 84086632 11912 5 83557023
84105175
11869 5 83521923 84089603 11913 5 83557023
84251635
11870 5 83521923 84104814 11914 5 83557023
84252180
11871 5 83521923 84105175 11915 5 83557023
84253030
11872 5 83521923 84251635 11916 5 83557023
84254208
11873 5 83521923 84252180 11917 5 83957023
84314930
11874 5 83521923 84253030 11918 5 83557023
84340523
11875 5 83521923 84254208 11919 5 83557023
84516340
11876 5 83521923 84314930 11920 5 83557023
84706916
11877 5 83521923 84340523 11921 5 83557023
84799488
11878 5 83521923 84516340 11922 5 83557023
84801081
11879 5 83521923 84706916 11923 5 83557023
84824103
11880 5 83521923 84799488 11924 5 83557023
84824203
11881 5 .83521923 84801081 11925 '5 83557023
84824816
11882 5 83521923 84824103 11926 5 83557023
84825422
11883 5 83521923 84824203 11927 5 83557023
84825763
11884 5 83521923 81824816 11928 5 83557023
84825942
11885 5 83521923 84825422 11929 5 83557023
84843411
11886 5 83521923 84825763 11930 5 83557023
84936441
11887 5 83521923 84825942 11931 5 83557023
84936493
11888 5 83521923 81843411 11932 5 83557023
84943705
11889 5 83521923 84936441 11933 5 83557023
169454950
11890 5 83521923 84936493 11934 5 83557023
181522829
245
CA 0 2 9 3 95 8 0 2 0 1 6 ¨ 08 ¨ 11
WO 2015/127248
PCT/US2015/016877
=
Table 1 (cont'd.)
Chromosomal Chmmosmmd
Segment Cht Boundaryl Boundmy2 Segment Chr. Boundary! Boundary2
11935 5 835571323 204759879 11979 5 83567769
83745342
11936 5 83557023 209874191 11980 5 83567769
83861275
11937 5 83560204 83567769 11981 5 83567769 83861633
11930 5 83560204 83572400 11982 5 83567769 83865653
11939 5 83560204 83607661 , 11983 5 83567769
83865914
11940 5 83560204 83745342 11984 9 81567769 83865920
11941 5 83560204 83861275 11985 5 83567769 83868010
11942 5 83560204 83861633 11986 5 83567769 84019752
11943 5 83560204 83865653 11987 5 83567769 84065912
11944 5 83560204 83865914 11988 5 83567769 84086632
11945 5 83560204 83865920 11989 5 83567769 84089601
11946 5 83560204 83868010 11990 5 83567769 84104814
11947 5 88560204 84019752 11991 5 83567769
84105175 =
11948 5 83560204 84065912 11992 5 83567769 84251635
11949 5 83560204 84086632 11993 5 83567769 84252180
11950 5 83560204 84089603 11994 5 83567769 84253030
11951 5 83560204 84104814 11995 5 83567769 84254208
11952 5 83560204 84105175 11996 5 83567769 84314930
11953 5 83560204 84251635 11997 5 83567769 84340523
11954 5 83560204 84252180 11998 5 83567769 04516340
11955 5 83560204 84253030 11999 5 83567769 84706916
11956 5 83560204 84254208 12000 5 83567769 84799488
11957 5 83560204 84314930 12001 5 83567769 84801081
11958 5 83560204 84340523 12002 5 83567769 84824103
11959 5 83560204 84516340 12003 5 83567769 84824203
11960 5 83560204 84706916 12004 5 83567769 84824816
11961 5 83560204 84799488 12005 5 83567769 84825422
11962 5 83560204 84801081 12006 5 83567769 84825763
11963 5 83560204 84824103 12007 5 83567769 84825942
11964 5 83560204 84824203 12008 5 83567769 84843411
11965 5 83560204 84824816 12009 5 83567769 84936441
11966 5 83560204 84825422 12010 5 83567769 84936493
11967 5 83560204 84825763 12011 5 83567769 84943705
11968 5 83560204 84825942 12012 5 83567769
169454950
11969 5 83560204 84843411 12013 5 83567769
181522829
11970 5 83560204 84936441 12014 5 83567769
284759879
11971 5 83560204 84936493 12015 5 83567769
209874191
11972 5 83560204 84943705 12016 5 83606990 83607661
11973 5 83560204 169454950 12017 5 83606990
83745342
11974 5 83560204 181522829 12018 5 83606990
83861275
11975 5 83560204 204759879 12019 5 83606990
83861633
11976 5 83560204 209874191 12020 5 83606990
83865651
11977 5 83567769 83572400 12021 5 83606990 83865914
11978 5 83567769 83607661 12022 5 83606990 83865920
246
CA 02 9 3 95 8 0 2 0 16 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosmnal Chromosomal
Segment Chr. Boondaryl Boundary2 Segment Chr. Bouodary1 Boundary2
12023 5 83606990 83868010 12067 5 83743980
84251635
12024 5 83606990 84019752 12068 5 83743980
84252180
12025 5 83606990 84065912 12069 5 83743980
84253030
12026 5 83606990 84086632 12070 5 83743980
84254208
12027 5 83606990 84089603 12071 5 83743980
84314930
12028 5 83606990 84104814 12072 5 83743980
84340523
12029 5 83606990 84105175 12073 5 83743980
84516340
12030 5 83606990 84251635 12074 5 83743980
84706916
12031 5 83606990 84252180 12075 5 83743980
84799488
12032 5 83606990 84253030 12076 5 83743980
84801081
12033 5 83606990 84254208 12077 5 83743980
84824103
12034 5 83606990 84314930 12078 5 83743980
84824203
12035 5 83606990 84340523 12079 5 83743980
84824816
12036 5 83606990 84516340 12080 5 83743980
84825422
12037 5 83606990 84706916 12081 5 83743980
81825763
12038 5 83606990 84799488 12082 5 83743980
84825942
12039 5 83606990 84801081 12083 5 83743980
84843411
12040 5 83606990 04824103 12084 5 83743980
84936441
12041 5 83606990 84824203 12085 5 83743980
84936493
12042 5 83606990 84824816 12086 5 83743980
84943705
12043 5 83606990 84825422 12087 5 83743980
169454950
12044 5 83606990 84825763 12088 5 83743980
181522829
12045 5 83606990 84825942 12089 5 83743980
204759879
12046 5 83606990 84843411 12090 5 83743980
209874191
12047 5 83606990 84936441 12091 5 83859479
83861275
12048 5 83606990 84936493 12092 5 83859479
83861633
12049 5 83606990 84943705 12093 5 83859479
83865653
12050 5 83606990 169454950 12594 5 83859479
83865914
12051 5 83606990 181522829 12095 5 83859479
83865920
12052 5 83606990 204759879 12096 5 83859479
83868010
12053 5 83606990 209874191 12097 5 83859479
84019752
12054 5 83743980 83745342 12098 5 83859479
84065912
12055 5 83743980 83861275 12099 5 83859479
84086632
12056 5 83743980 83861633 12100 5 83859479
84089603
12057 5 83743980 83865653 12101 5 83859479
84104814
12058 5 83743980 83865914 12102 5 83859479
84105175
12059 5 83743980 83865920 12103 5 83859479
84251635
_
12060 5 83743980 83868010 12104 5 83859479
84252180
12061 5 83743980 84019752 12105 5 83859479
84253030
. 12062 5 83743980 84065912 12106 5 83859479
84254208
12063 5 83743980 84086632 12107 5 83859479
84314930
12064 5 83743980 84089603 12108 5 83859479
84340523
12065 5 83743980 84104814 12109 5 83859479
84516340
12066 5 81743980 84105175 12110 5 83859479
84706916
247
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 Bouadary2 Sogmeat Chr.
Boundaryl Boundmy2
12111 5 83859479 84799488 12155 5 83860797
84936493
12112 5 83859479 84801081 12156 5 83860797
84943705
12113 5 83859479 84824103 12157 5 83860797
169454950
12114 5 83859479 84824203 12158 5 83860797
181522829
12115 5 83859479 84824816 12159 5 83860797
204759879
12116 5 83859479 84825422 12160 5 83860797
209874191
12117 5 83859479 84825763 12161 5 83861275
83861394
12118 5 83859479 84825942 12162 5 83861275
83865653
12119 5 83859479 84843411 12163 5 83861275
83865914
12120 5 83859479 84936441 12164 5 83861275
83865920
12121 5 83859479 84936493 12165 5 83861275
83868010
12122 5 83859479 84943705 12166 5 83861275
84019752
12123 5 83859479 169454950 12167 ' 5
83861275 84065912
12124 5 83859479 181522829 12168 5 83861275
84086632
12125 5 83859479 244759879 12169 5 83861275
84089603
12126 5 83859479 209874191 12170 5 83861275
84104814
12127 5 83860797 03865653 12171 5 83861275
84105175
12128 5 83860797 83865914 12172 5 83861275
84251635
12129 5 83860797 83865920 12173 5 83861275
84252180
12130 5 83860797 83868010 12174 5 83861275
04253030
12131 5 83860797 84019752 12175 5 83861275
84254208
12132 5 83860797 84065912 12176 5 83861275
84314930
12133 5 83860797 84086632 12177 5 83861275
84340523
12134 5 83860797 84089603 12178 5 83861275
84516340
12135 5 83860797 84104814 12179 5 83861275
84706916
12136 5 83860797 84105175 12180 5 83861275
84799488
12137 5 83860797 84251635 12181 5 83861275
84801081
12138 5 83860797 84252180 12182 5 83861275
84824103
12139 5 83860797 84253030 12183 5 83861275
84824203
12140 5 83860797 84254208 12184 5 83861275
84824816
12141 5 83860797 84314930 12185 5 83861275
84825422
12142 5 83860797 84340523 12186 5 83861275
84823763
12143 5 83860797 84516340 12187 5 83861275
84825942
12144 5 83860797 84706916 12188 5 83861275
84843411
12145 5 83860797 84799488 12189 5 83861275
84936441
12146 5 83860797 84801081 12190 5 83861275
84936493
12147 5 83860797 84824103 12191 5 83861275
84943705
12148 5 83860797 84024203 12192 5 83861275
169454950
12149 5 83860797 84824816 12193 5 83861275
181522829
12150 5 83860797 , 84625422 12194 5 83861275
204759879
12151 5 83860797 84825763 12195 5 83861275
209874191
12152 5 83860797 84825942 12196 5 81861394
83865653
12153 5 83860797 84843411 12197 5 83861394
83865914
12154 5 83860797 84936441 12198 5 83861394
83865920
248
CA 02 9 3 958 0 2 0 16-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Chromosomal amnnosornal
Segment Chi. Boundary 1 Boondani2 Segment Om Boundary 1
Boundary2
12199 5 83861394 83868010 12243 5 83864692
84254208
12200 5 83861394 84019752 12244 5 83864692
84314930
12201 5 83861394 84065912 12245 5 83864692
84340523
12202 5 83861394 84086632 12246 5 83864692
84516340
12203 5 83861394 84089603 12247 5 83864692
84706916
12204 5 83861394 84104814 12248 5 83864692
84799488
12205 5 83861394 84105175 12249 5 83864692
84801061
12206 5 83861394 84251635 12250 5 83864692
84824103
12207 5 83861394 84252180 12251 5 83864692
84824203
12208 5 83861394 84253030 12252 5 83864692
84824816
12209 5 83861394 84254208 12253 5 83864692
84825422
12210 5 83861394 84314930 12254 5 83864692
64825763
12211 5 83861394 84340523 12255 5 83864692
84825942
12212 5 83861394 84516340 12256 5 83864692
84843411
12213 5 83861394 84706916 12257 5 83864692
84936441
12214 5 83861394 84799488 12258 5 83864692
84936493
12215 5 83861394 84801081 12259 5 83864692
84943705
12216 5 83861394 84824103 12260 5 83864692
169454950
12217 5 83861394 84824203 12261 5 83864692
181522829
12218 5 83861394 84824816 12262 5 83864692
204759879
12219 5 83661394 84825422 12263 5 83864692
209874191
12220 5 83861394 84825763 12264 5 83867332
83868010
12221 5 83861394 84825942 12265 5 83867332
84019752
12222 5 83861394 64843411 12266 5 83867332
84065912
12223 5 83861394 84936441 12267 5 83867332
84086632
12224 5 83861394 84936493 12268 5 83867332
84089603
12225 5 83861394 84943705 12269 5 83867332
84104814
12226 5 83861394 169454950 12270 5 83867332
84105175
12227 5 83861394 181522829 12271 5 83867332
84251635
12228 5 83861394 204759879 12272 5 83867332
84252180
12229 5 83861394 209874191 12273 5 83867332
84253030
12230 5 83864692 83865653 12274 5 83867332
84254208
12231 5 83864692 83865914 12275 5 83867332
84314930
12232 5 83864692 83865920 12276 5 83867332
84340523
12233 5 83864692 83868010 12277 5 83867332
84516340
12234 5 83864692 84019752 12278 5 83867332
84706916
12235 5 83864692 84065912 12279 5 83867332
84799488
12236 5 83864692 84086632 12280 5 83867332
84801081
12237 5 83864692 84089603 12281 5 83867332
84824103
12238 5 83864692 84104814 12282 5 83867332
84824203
12239 5 83864692 84105175 12283 5 83867332
84824816
12240 5 83864692 , 84251635 12284 5 83867332
84825422
12241 5 83864692 84252180 12285 5 83867332
84825763
12242 5 83864692 84253030 12286 5 83867332
84825942
249
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chnumweima Chromosomal
Segment Chr. Boundary 1 Boundary2 Segment Ch,. Boundanfl
Boundary 2
12287 5 83867332 84843411 12331 5 84061561
84252180
12288 5 83867332 84936441 12332 5 84061561
84253030
12289 5 83867332 84936493 12333 5 84061561
84254208
12290 5 83867332 84943705 12334 5 84061561
84314930
12291 5 83867332 169454950 12335 5 84061561
84340523
12292 5 83867332 181522829 12336 5 84061561
84516340
12293 5 83867332 204759879 12337 5 84061561
84706916
12294 5 83867332 209874191 12338 5 84061561
84799488
12295 5 84018779 84019752 12339 5 84061561
84801081
12296 5 84018779 84065912 12340 5 84061561
84824103
12297 5 84018779 84086632 12341 5 84061561
84824203
12298 5 84018779 84089603 12342 5 84061561
84824816
12299 5 84018779 84104814 12343 5 84061561
84825422
12300 5 84018779 84105175 12344 5 84061561
84825763
12301 5 84018779 84251635 12345 5 84061561
84825942
12302 5 84018779 84252180 12346 5 84061561
84843411
12303 5 84018779 84253030 12347 5 84061561
84936441
12304 5 84018779 84254208 12348 5 84061561
84936493
12305 5 84018779 84314930 12349 5 84061561
84943705
12306 5 84018779 84340523 12350 5 84061561
169454950
12307 5 84018779 84516340 12351 5 84061561
181522829
12308 5 84018779 84706916 12352 5 84061561
204759879
12309 5 84018779 84799488 12353 5 84061561
209874191
12310 5 84018779 84801081 12354 5 84083388
84086632
12311 5 84018779 84824103 12355 5 84083388
84089603
12312 5 84018779 84824203 12356 5 84083388
84104814
12313 5 84018779 84824816 12357 5 84083388
84105175
12314 5 84018779 84825422 12358 5 840141318
84251635
12315 5 84018779 84825763 12359 5 84083388
84252180
12316 5 84018779 84825942 12360 5 84083388
84253030
12317 5 84018779 84843411 12361 5 84083388
84254208
12318 5 84018779 84936441 12362 5 84083388
84314930
12319 5 84018779 84936493 12363 5 84083388
84340523
12320 5 84018779 84943705 12364 5 84083388
84516340
12321 5 84018779 169454950 12365 5 84083388
84706916
12322 5 84018779 181522829 12366 5 84083388
84799488
12323 5 84018779 204759879 12367 5 84083388
84801081
12324 5 84018779 209874191 12368 5 84083388
84824103
12325 5 84061561 84065912 12369 5 84083388
84824203
12326 5 84061561 84086632 12370 5 84083388
84824816
12327 5 14061561 84089603 12371 5 84083388
84825422
12328 5 84061561 14104814 12372 5 84083388
84825763
12329 5 84061561 84105175 12373 5 84083388
84825942
12330 5 84061561 84251635 12374 5 84083388
84843411
250
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chromosomal
Segment Chn Boundary 1 Boundary2 Segment (In Boundary1
Boundary 2
12375 5 84083388 84936441 12419 5 84101452
84799488
12376 5 84083388 84936493 12420 5 84101452
84801081
12377 5 84083388 84943705 12421 5 84101452
84824103
12378 5 84083388 169454950 12422 5 84101452
84824203
12379 5 84083388 181522829 12423 5 84101452
84824816
12380 5 84083388 204759879 12424 5 84101452
84825422
12381 5 84083388 209874191 12425 5 04101452
84825763
12382 5 84088707 84089603 12426 5 84101452
84825942
12383 5 84088707 84104814 12427 5 84101452
84843411
12384 5 84088707 84105175 12428 5 84101452
84936441
12385 5 84088707 84251635 12429 5 84101452
84936493
12186 5 84088707 84252180 12430 5 84101452 ,
84943705
12387 5 84088707 84253030 12431 5 84101452
169454950
12388 5 84088707 84254208 12432 5 84101452
181522829
12389 5 84088707 84314930 12433 5 84101452
204759879
12390 5 84088707 84340523 12434 5 84101452
209874191
12391 5 84088707 84516340 12435 5 84103364
84104814
12392 5 84088707 84706916 12436 5 84103364
84105175
12393 5 84088707 84799488 12437 5 84103364
84251635
12394 5 84088707 84801081 12438 5 84103364
84252180
12395 5 84088707 84824103 12439 5 84103364
84253030
12396 5 84088707 84824203 12440 5 84103364
84254208
12397 5 84088707 84824816 12441 5 84103364
84314930
12398 5 84088707 84825422 12442 5 84103364
84340523
12399 5 84088707 84825763 12443 5 84103364
84516340
12400 5 84088707 84825942 12444 5 84103364
84706916
12401 5 84088707 84843411 12445 5 84103364
84799488
12402 5 84088707 84936441 12446 5 84103364
84801081
12403 5 84088707 64936493 12447 5 84103364
84824103
12404 5 84088707 84943705 12448 5 84103364
84824203
12405 5 84088707 169454950 12449 5 84103364
84824816
12406 5 84088707 181522829 12450 5 84103364
84825422
12407 5 84088707 204759879 12451 5 84103364
84825763
12408 5 84088707 209874191 12452 5 84103364
84825942
12409 5 84101452 84104814 12453 5 84103364
84843411
12410 5 84101452 84105175 12454 5 84103364
84936441
12411 5 84101452 84251635 12455 5 84103364
84936493
12412 5 84101452 84252180 12456 5 84103364
84943705
12413 5 84101452 84253030 12457 5 84103364
169454950
12414 5 84101452 84254208 12458 5 84103364
181522829
12415 5 84101452 84314930 12459 5 84103364
204759879
12416 5 84101452 84340523 12460 5 84103364
209874191
12417 5 84101452 84516340 12461 5 84248220
84251635
12418 5 84101452 84706916 12462 5 84248220
84252180
251 =
CA 02 9 3 95 8 0 2 0 16 ¨08 ¨11
WO 2015/127248
PCT/US2015/016877
Table 1 (contd.)
Chromosomal Chrmnomal
Segment Chn Boundary 1 Bounghey2 Segment CM. B005dary1
Boundary2
12463 5 84248220 84253030 12507 5 84248224 204759879
12464 5 84248220 84254208 12508 5 84248224
209874191
12465 5 84248220 84314930 12509 5 84252053
84252180
12466 5 84248220 84340523 12510 5 84252053
84253030
12467 5 84248220 84516340 12511 5 84252053
84254208
12468 5 84248220 84706916 12512 5 84252053
84314930
12469 5 84248220 84799488 12513 5 84252053
84340523
12470 5 84248220 84801081 12514 ' 5 84252053
84516340
12471 5 84248220 84824103 12515 5 84252053
84706916
12472 5 84248220 84824203 12516 5 84252053
84799488
12473 5 84248220 84824816 12517 5 84252053
84801081
12474 5 84248220 84825422 12518 5 84252053
84824103
12475 5 84248220 84825763 12519 ' 5 84252053
84824203
12476 5 84248220 84825942 12520 5 84252053
84824816
12477 5 84248220 84843411 12521 5 84252053
84825422
12478 5 84248220 84936441 12522 5 84252053
84825763
12479 5 84248220 84936493 12523 5 84252053
84825942
12480 5 84248220 84943705 12524 5 84252053
84843411
12481 5 84248220 169454950 12525 5 84252053
84936441
12482 5 84248220 181522829 12526 5 84252053
84936493
12483 5 84248220 204759879 12527 5 84252053
84943705
12464 5 84248220 209874191 12528 5 84252053
169454950
12485 5 84248224 84251635 12529 5 84252053
181522829
12486 5 84248224 84252180 12530 5 84252053
204759879
12487 5 84248224 84253030 12531 5 84252053
209874191
12488 5 84248224 84254208 12532 5 84253581
84254208
12489 5 84248224 84314930 12533 5 84253581
84314930
12490 5 84248224 84340523 12534 5 84253581
84340523
12491 5 84248224 84516340 12535 5 84253581
84516340
12492 5 84248224 84706916 12536 5 84253581
84706916
12493 5 84248224 84799488 12537 5 84253581
84799488
12494 5 84248224 84801081 12538 5 84253581
84801081
12495 5 84248224 84824103 12539 5 84253581
84824103
12496 5 84248224 84824203 12540 5 84253581
84824203
12497 5 84248224 84824816 12541 5 84253581
84824816
12498 5 84248224 84825422 12542 5 84253581
84825422
12499 5 84248224 84825763 12543 5 81253581
84825763
12500 5 84248224 84825942 12544 5 84253581
84825942
12501 5 84248224 84843411 12545 5 84253581
84843411
12502 5 84248224 84936441 12546 5 84253581
84936441
12503 5 84248224 84936493 12547 5 84253581
84936493
12504 5 84248224 84943705 12548 5 84253581
84943705
12505 5 84248224 169454950 12549 5 84253581
169454950
12506 5 84248224 181522829 12550 5 84253581
181522829
252
CA 02 93 958 0 2 016 ¨08-11
WO 2015/127248
PCT/US2015/016877
Table 1 (cont'd.)
Clumnosomal Clmmulsonud
Segment Chr. Boundar3r1 Bomulary2 Segment Chg. Boundaryl
Boon3ary2
12551 5 84253581 204759879 12595 5 84516113
84801081
12552 5 84253581 209874191 12596 5 84516113
84824103
12553 5 84314151 84314930 12597 5 84516113
84824203
12554 5 _84314151 84340523 12598 5 84516113
84824816
12555 5 84314151 84516340 12599 5 84516113
84825422
12556 5 84314151 84706916 12600 5 84516113
84825763
12557 5 84314151 84799488 12601 5 84516113
84825942
12558 5 84314151 84801081 12602 5 84516113
84843411
12559 5 84311151 84824103 12603 5 84516113
84936441
12560 5 84314151 84824203 12604 5 84516113
84936493
12561 5 84314151 84824816 12605 5 84516113
84943705
12562 5 84314151 84825422 12606 5 84516113
169454950
12563 5 84314151 84825763 12607 5 84516113
181522829
12564 5 84314151 84825942 12608 5 84516113
204759879
12565 5 84314151 84843411 12609 5 84516113
209874191
12566 5 84314151 84936441 12610 5 84706267
84706916
12567 5 84314151 84936493 12611 5 84706267
84799488
12568 5 84314151 84943705 12612 5 84706267
84801081
12569 5 84314151 169454950 12613 5 84706267
84824103
12570 5 84314151 181522829 12614 5 84706267
84824203
12571 5 84314151 204759879 12615 5 84706267
84824816
12572 5 84314151 209374191 12616 5 84706267
14825422
12573 5 84338664 84340523 12617 5 84706267
84825763
12574 5 84338664 84516340 12618 5 84706267
84825942
12575 5 84338664 84706916 12619 5 84706267
84843411
12576 5 84338664 84799488 12620 5 84706267
84936441
12577 5 84338664 84801081 12621 5 84706267
84936493
12578 5 84338664 84824103 12622 5 84706267
84943705
12579 5 84338664 84824203 12623 5 84706267
169454950
12580 5 84338664 84824816 12624 5 84706267
181522829
12581 5 84338664 84825422 12625 5 84706267
204759879
12582 5 84338664 84825763 12626 . 5 84706267
209874191
12583 5 84338664 84825942 12627 5 84796405
84799488
12584 5 84338664 84843411 12628 5 84796405
84801081
12585 5 84338664 84936441 12629 5 84796405
84824103
12586 5 84338664 84936493 12630 5 84796405
84824203
12587 5 84338664 84943705 12631 5 84796405 84824816 '
12588 5 84338664 169454950 12632 5 84796405
84825422
12589 5 84338664 181522829 12633 5 84796405
84825763
12590 5 84338664 204759879 12634 5 84796405
84825942
12591 5 84338664 209874191 12635 5 84796405
84843411
12592 5 84516113 84516340 12636 5 84796405
84936441
12593 5 84516113 84706916 12637 5 84796405
84936493
12594 5 84516113 84799488 12638 5 84796405
84943705
253
CA 0 2 9 3 95 8 0 2 0 1 6 -08 -11
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PCT/US2015/016877
Table 1 (contd.)
aranosomal Chnunosonal
Segment Chn Boundary1 Boundary2 Segment Chn Boundary1 Boundary2
12639 5 84796405 169484950 12683 5 84822183
181522829
12640 9 84796405 181522829 12684 5 84822113
204759879
12641 5 84796405 204759879 12685 5 84822183
209874191
12642 5 84796405 2091174191 12686 5 84822215
84824103
12641 5 84799805 84801081 12687 5 84822215
84824203
12644 5 84799805 84824103 12688 5 84822215
84824816
12645 5 84799805 84824201 12689 5 84822215
84E25422
12646 5 84799805 84824816 12690 5 84822215
84825763
12647 5 84799805 84825422 12691 5 84822215
84825942
12648 5 84799805 84825763 12692 5 84822215
84843411
12649 5 84799805 84825942 12693 5 84822215
84936493
12650 5 84799E105 84843411 12694 5 84822215
84943705
12651 5 84799805 84936441 12695 5 84822215
169454950
12652 5 84799805 84936493 12696 5 84822215
181522829
12653 5 84799805 84943705 12697 5 84822215
204759879
12654 5 84799805 169454950 12698 5 84822215
209874191
12655 5 84799805 161522829 12699 5 84824103
84824203
12656 5 84799805 204759879 12700 5 84824103
84824816
12657 5 84799805 209874191 12701 5 84824103
84840183
12658 5 84821810 84824103 12702 5 84824103
84843411
12659 5 84821810 84824203 12703 5 84824103
84936441
12660 5 84821810 84824816 12704 5 84824103
84936493
12661 5 84821810 84825422 12705 5 84824103
84943705
12662 5 84821810 84825763 12706 5 84824103
169454950
12663 5 84821810 84825942 12707 5 84824103
181522829
12664 5 84821810 84843411 12708 5 84824103
204759879
12665 5 84821810 84936441 . 12709 5 84824103
209874191
12666 5 84821810 84936493 12710 5 84824203
84934242
12667 5 84821810 84943705 12711 5 84824203
84936441
12668 5 84821810 169454950 12712 5 84824203
84936493
12669 5 84821810 181522829 12713 5 84824203
84943705
12670 5 84821810 204759879 12714 5 84824203
169454950
12671 5 84821810 209874191 12715 5 84824203
181522829
12672 5 84822183 84824103 12716 5 84824203
204759879
12673 5 84822183 84824203 12717 5 84824203
209874191
12674 5 84822183 84824816 12718 5 84840183
84843411
12675 5 84822183 84825422 12719 5 84840183
84936441
12676 5 84822183 84025763 12720 5 84840183
84936493
12677 5 84822183 84825942 12721 5 84840183
84943705
12678 5 84822183 84843411 12722 5 84840183
169454950
12679 5 84822183 84936441 12723 5 84840183
181522829
12680 5 84822183 84936493 12724 5 84840183
204759879
12681 5 84822183 84943705 12725 5 84840183
209874191
12682 5 84822183 169454950 12726 5 84934242
84936441
254
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Table 1 (cont'd.)
Chromosomal Chromosomal
Segment Chr. Boundary 1 13ouneary2 Segment Chr.
Boundary1 Boundmy2
12727 5 84934242 84936493 12748 6 165317744
167541488
12728 5 84934242 84943705 12749 6 165632140
167541488
12729 5 84934242 169454950 12750 7 17293606
33157904
12730 5 84934242 181522829 12751 7 17293606
52027945
12731 5 84934242 204759879 12752 7 17293606
114050244
12732 5 84934242 209874191 12753 7 33157904
52027945
12733 5 84938287 84943705 12754 7 33157904
134050244
12734 5 84938287 169454950 12755 7 52027945
134050244
12735 5 84938287 181522829 12756 8 120061025
173714727
12736 5 84938287 204759879 12757 9 23258800
128947590
12737 5 84938287 209874191 12758 9 23258800
145336391
12738 5 169454950 181522829 12759 9 23258800
147896266
12739 5 169454950 204759879 12760 9 128947590
145336391
12740 5 169454950 209874191 12761 9 128947590
147896266
12741 5 181522829 204759879 12762 9 145336391
147896266
12742 5 181522829 209874191 12763 10 5873450
140850928
12743 5 204759679 209874191 12764 10 5873450
142092409
12744 6 121671402 165317744 12765 10 5873450
145273700
12745 6 121671402 165632140 12766 10 140850928
142092409
12746 6 121671402 167541488 12767 10 140850928
145273700
12747 6 165317744 165632140 12768 10 142092409
145273700
Table 2. Examples of alleles associated with increased fertility in maize.
Desired Desired Desired
Chr, Position Allele Cbr. Position Allele Chr. Position
Allele
77990414 A 5 79859447 A 5 80389419 C
5 77990442 C 5 79862605 G 5 80389432 A
5 77990478 T 5 79862609 A 5 80389533 C
5 77990499 A 5 79865888 T 5 80804587 G
5 77990523 G 5 79867527 A 5 80828757 C
5 77990545 A 5 80236641 G 5 80829669 T
5 77991998 G 5 80236734 T 5 81267278 G
5 77995135 C 5 80236789 T 5 81267320 T
5 77995150 A 5 80236810 T 5 81763802 G
5 77996710 T 5 80236933 T 5 81763824 C
5 78310107 A 5 80271911 A 5 81802220 A
5 78310132 T 5 80279798 C 5 81802574 C
5 78918620 G 5 80387964 C 5 81950558 T
5 79531947 A 5 80388968 T 5 81950582 T
5 79537908 G 5 80389273 A 5 82085147 C
5 79707038 C 5 80389290 C 5 82087667 A
5 79707074 A 5 80389380 C 5 82235558 A
255
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Table 2 (coact)
Desired Desired Desired
Chn Position Allele Chn Position Allele an Position Allele
82236085 T 5 82549380 C 5 84824103 T
5 82236162 A 5 82549409 A 5 84824205 T
5 82325775 C 5 82549517 A 5 84824447 C
5 82325977 C 5 82549554 C 5 84824473 C
5 82326020 G 5 82549629 C 5 84824495 G
5 82326037 G 5 82549650 C 5 84824561 G
5 82326164 C 5 82549724 C 5 84824603 C
5 82326170 T 5 82549867 C 5 84824951 i
5 82326175 T 5 82549995 G 5 84825014 C
5 82423926 A 5 82550364 C 5 84825020 A
5 82424010 G 5 82550459 G 5 84825024 G
5 82424392 A 5 82550498 G 5 84825087 C
5 82424461 C 5 82550853 T 5 84825264 T
5 82424629 G 5 82550983 T 5 84825276 T
5 82424695 C 5 82551025 C 5 84825303 C
5 82424706 C 5 82552120 T 5 84825469 G
5 82424752 G 5 82552368 G 5 84825471 A
5 82424773 G 5 82553234 G 5 84825480 C
5 82424791 A 5 82555338 A 5 84825497 G
5 82425070 C 5 83560144 T 5 84825510 C
5 82425098 C 5 83560192 A 5 84825512 A
5 82425358 G 5 83860601 T 5 84825527 C
5 82443847 T 5 83860682 T 5 84825551 G
5 82443957 T 5 83861161 G 5 84825588 G
5 82443978 AJG 5 83861215 A 5 84825642 C
5 82444245 T 5 83861266 A 5 84841805 T
5 82444266 T 5 83861344 T 5 84842085 A
5 82444716 A 5 83861361 T 5 84843056 A
5 82445340 A 5 84086015 T 5 84938414 T
5 82445493 A 5 84796702 G 5 84938476 T
5 82446188 C 5 84822534 G 5 84938528 T
5 82446660 G 5 84822543 T
5 82446684 T 5 84823992 A
5 82446704 A 5 84823998 C
Table 3. Examples of proteins of interest encoded by maize chromosome 5.
SEQ ID SE Q ID SEQ ID
Protein Identifier Chr. Positions Strand NO: NO: NO:
GRMZM2G435796 P01 5 78022476 - 78023096 - 1 176 351
GRMZM5 G832780 P01 5 78129898 - 78131652 - 2 177 352
GRM1ZM2 G425559_PO 1 5 78129898 - 78131784 + 3 178 353
GRMZM2G006937 P01 5 78255163 - 78310499 + 4 179 354
GRMZM2G102912_P 0 1 5 78380304 - 78381593 + 5 180 355
256
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Table 3 (cont'cl)
SEQ ID SEQ ID SEQ ID
Protein Identifier Chr. Positions Strand NO: NO: NO:
GRMZM2G102845_PO1 5 78381834 - 78389884 - 6 181 356
0RMZM50865367_P01 5 78519893 - 78520683 + 7 182 357
GRMZM2G322493_P01 5 78758856 - 78765635 + 8 183 358
GRM/M2G167741_P01 5 78772058 - 78780292 + 9 184 359
GRMZM2G410357 _P02 5 78804756 - 78813114 + 10 185 360
0RMZNI2G410357_PO1 5 78804756-78814710 + 11 186 361
GRMZ.M2 G410357 _PO4 5 78805059 - 78815306 + 12 187 362
GR14ZM2G410357 PO3 5 78805059 - 78815306 + 13 188 363
GRMZM2G410357 PO5 5 78805059 - 78815306 + 14 189 364
GRWM2G410357_P06 5 78814424 - 78814976 I 15 190 365
GRMZM20410393 PO3 5 78819803 - 78826528 + 16 191 366
GRMZM2G410393_PO4 5 78819803-78826528 -F 17 192 367
0RMZ,1V120410393 PO5 5 78819803 - 78826528 + 18 193 368
GRMZM20410393 PO2 5 78819803 - 78826538 -F 19 194 369
GRMZM2G410393 P01 5 78819803 - 78826612 + 20 195 370
AC197118.3 FGP005 5 78820119 - 78821393 - 21 196 371
GRMZM2G133048_PO1 5 78904639 - 78918850 + 22 197 372
GRMZM2G018686_PO1 5 79055654 - 79056960 - 23 198 373
AC212103.3 FGP002 5 79162381 - 79163631 + 24 199 374
AC193606.2_FGP001 5 79175814 - 79176557 - 25 200 375
0RIVI/M2G332749 P01 5 79183135 - 79188028 + 26 201 376
GRMZM20068176 POI 5 79200056 - 79201760 - 27 202 377
GRMZM2G369391_PO1 5 79229010 - 79230318 + 28 203 378
G1tMZM2G369396 P01 5 79229019-79230005 - 29 204 379
0RMZM2G314233 P01 5 79503885-79505592 4- 30 205 380
GRMZM5G816609 P01 5 79505757 - 79510072 + 31 206 381
GRMZM20063942_P06 5 79531009 - 79538012 + 32 207 382
G1UMZM2G063942_P03 5 79531009 - 79538048 + 33 208 383
0RMZM2G063942 PO2 5 79531009 - 79538048 + 34 209 384
GRMZM20063942_P01 5 79531009 - 79538048 + 35 210 385
0RMZM2G063942 PO8 5 79531040 - 79538012 h 36 211 386
GRMZM20063942 P07 5 79531040 - 79538012 + 37 212 387
G1tMZM2G063942_1'04 5 79531040 - 79538048 t 38 213 388
GRMZM2G063942_PO5 5 79537564 - 79538048 + 39 214 389
0RMZM5G853950 P01 5 79666742-79669824 I 40 215 390
GRMZM20472708 P01 5 79679654-79682242 - 41 216 391
GRMZM2G033138_PO4 5 79697555 - 79699261 + 42 217 392
GRMZM2G033138 PO3 5 79697555 - 79710673 + 43 218 393
GRMZM20033138_P01 5 79697555 - 79710673 + 44 219 394
G11MZM20033138_P02 5 79697555 - 79710673 + 45 220 395
GRMZM20062885 P01 5 79857859 - 79861902 + 46 221 396
0RMZ.M20062914_P03 5 79862405 -79867710 - 47 222 397
GRMZM2G062914_P02 5 79862405 -79867868 - 48 223 398
GR1vIZM213062914_1,01 5 79862405-79867873 - 49 224 399
257
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Table 3 (cont'cl)
SEQ ID SEQ ID SEQ ID
Protein Identifier Chr. Positions Strand NO: NO: NO:
0RMZM50865405_P01 5 79960831-79961961 - 50 225 400
GRIVL7M2G353478_P01 5 80084956-80086268 - 51 226 401
0RMZM20067313_PO1 5 80187987-80190673 + 52 227 402
GRMZM2G067313_P02 5 80188978- 80190777 + 53 228 403
GRMZM2G367431 P01 5 80191781-80192546 + 54 229 404
GRM1M20067350_1"01 5 80195077-80199923 - 55 230 405
GRMZM2G067350_P02 5 80195714 - 80199923 - 56 231 406
GRMZM2C1O3 I 850 P01 5 80236478 - 80241911 - 57 232 407
0RMZM20031850 PO2 5 80238986 - 80241911 - 58 233 408
GRM2M213031850 PO3 5 80239243 - 80241911 - 59 234 409
G1tM7M2G024612_P01 5 80273499-80282785 - 60 235 410
GRMZM50852229 P01 5 80344025-80345337 + 61 236 411
0RMZM5G829894_P01 5 80387639 - 80389787 + 62 237 412
GRNIZM56829894 PO2 5 80387639 - 80389787 + 63 238 413
GRMZ945G829894_P03 5 80388596 - 80389787 + 64 239 414
AC233959.1 FGP003 5 80411337-80411639 - 65 240 415
GRMZM20701675 P01 5 80446281-80446855 + 66 241 416
AC233959.1 FGP006 5 80491807-80492790 - 67 242 417
GRMZ1v12G392320 PO2 5 80669160-80670554 + 68 243 418
GRMZM2G392320_POI 5 80669160-80674679 + 69 244 419
GRMZM2G147800_POI 5 80715081-80720509 + 70 245 420
- GRML:v12G093490 P01 5 80795990-80800856 - 71 246 421
GRMZM2G482256 P01 5 80803727-80807409 - 72 247 422
GRMZM2G425774_PO1 5 80828457-80835734 - 73 248 423
GRM71,42G425774_P02 5 80828945-80835734 - 74 249 424
GRMZM20165945 PO2 5 80969412-80972258 + 75 250 425
GRMZIVI2G165945_PO1 5 80969412-80974450 + 76 251 426
GRMZM20165945 PO3 5 80970381 -80974450 + 77 252 427
GRMZM2G400197_PO1 5 81031951-81047638 + 78 253 428
GRMZM2G104425201 5 81076870-81082921 - 79 254 429
GR0v1ZM5G887054 P01 5 81155197-81157909 - 80 255 430
0RM7M5G887054 PO2 5 81155255-81157909 - 81 256 431
GRM7M50887054_P03 5 81155675-81157909 - 82 257 432
GRMZM50887054 PO4 5 81156713-81157909 - 83 258 433
GRMZM2G088880_PO1 5 81265211-81267499 + 84 259 434
GRMZM2G088880_1P02 5 81265211-81267499 -I 85 260 435
GRMZM20088880 PO3 5 81265354 - 81267485 + 86 261 436
AC207104.3 FGP001 5 81273796 - 81274512 -I- 87 262 437
GRMZM26322672_P01 5 81761119-81763618 + 88 263 438
GRM7M20011888_PO1 5 81793777 - 81797217 + 89 264 439
GRMZM2G085513 P01 5 81798893 - 81800186 - 90 265 440
GRMZM2G085469 P01 5 81801973 - 81806213 - 91 266 441
GRMZM5G817948 P01 5 81858527 - 81859374 -4- 92 267 442
GRMZIvI5G897067 P01 5 81859618 -81861368 + 93 268 443
258
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Table 3 (cont'd)
SEQ ID SFQ ID SEQ ID
Protein Identifier Chr. Positions Strand NO: NO: NO:
AC199577.4 FGP004 5 81863099 - 81863686 - 94 269 444
0RWM5G823733 P01 5 81914498 - 81916850 + 95 270 445
GRMZM50812923 PO2 5 81950191 - 81954891 - 96 271 446
GRIV4ZM5G812923_P03 5 81950191 -81954891 - 97 272 447
GRMZM50812923_P01 5 81951639 - 81954891 - 98 273 448
GRMZM2G464846_PO1 5 81984901 - 81985250 i 99 274 449
GRMZM20024882 P01 5 82083639 - 82101253 - 100 275 450
GRMZM5G868120 PO2 5 82137780 - 82143124 - 101 276 451
GRMZM5G868120 P01 5 82139338 - 82143124 - 102 277 452
GRMZM50867030 POI 5 82234311 -82236318 -F 103 278 453
GRMZM2G409658_PO1 5 82423451 - 82427210 - 104 279 454
GRMZM2G111201_PO1 5 82427780-82431853 + 105 280 455
GRMZ/v12G409726_PO1 5 82443403 - 82446794 - 106 281 456
GRMZM2G409726 PO2 5 82443815-82446714 - 107 282 457
GRNIZM2G409726_003 5 82443856 - 82446714 - 108 283 458
GRMZM20005562_POI 5 82549227 - 82555670 - 109 284 459
GRMZM20005562 PO4 5 82549246-82552090 - 110 285 460
G1S.MZM2G005562 PO3 5 82549246-82555641 - 111 286 461
GRMZM20005562 PO2 5 82549246-82555641 - 112 287 462
GRMZM2G005562 PO5 5 82549299 - 82551111 - 113 288 463
GRMZM2G005562_P06 5 82554608-82555670 - 114 289 464
GRM1M2G005562_P07 5 82554971- 82555670 - 115 240 465
GRMZM2G006144 P01 5 82556313 - 82561535 - 116 291 466
GRIVIZM2G006144 PO2 5 82556337-82559047 - 117 292 467
0RMZM2G443332_P01 5 82609175 - 82610100 - 118 293 468
GRMZM2G167578_901 5 82675654-82676901 - 119 294 469
GRMZM5G844909_PO1 5 82675825-82676822 1 120 295 470
GRMZM2G390350_ P01 5 82882273-82883691 - 121 296 471
GRMZIM2G158520 P01 5 82953053-82954942 t 122 297 472
GRMZM2G459142 P01 5 82971168 - 82971688 + 123 298 473
0RMZM50844046 P01 5 83023500-83023965 - 124 299 474
GRMZM2G564932_PO1 5 83093332 - 83094205 + 125 300 475
AC197265.3_FGP005 5 83145879-83146355 P 126 301 476
GRMZM2G087267_P01 5 83277783 -83281412 + 127 302 477
GRMZM2G087267_P02 5 83277785 - 83281412 + 128 303 478
GRMZM2G087267_P03 5 83279034- 83280630 + 129 304 479
0RMZM2G032280 P01 5 83397014 - 83400242 + 130 305 480
GRMZM20087495_P01 5 83402967 - 83405797 - 131 306 481
GRMZM20387127_PO1 5 83435480 - 83437132 - 132 307 482
GRMZM5G889792_901 5 83521923 - 83522252 - 133 308 483
AC234515.1_FGP003 5 83557023 -83560095 + 134 309 484
AC234515.1_FGP002 5 83567769 - 83572400 + 135 310 485
GRMZM5G894416_P01 5 83606990 - 83607661 + 136 311 486
G1Uv1ZM20050080 P01 5 83743980-83745342 - 137 312 487
259
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Table 3 (cont'd)
SEQ 1D SEQ ID SEQ ID
Protein Identifier Om Positions Strand NO: NO: NO:
GRMZM2G088396_P01 5 83859479 - 83861633 + 138 313 488
6RMZM2G088235_P03 5 83860797 - 83865914 - 139 314 489
GRMZM2G088235_P02 5 83860797 - 83865920 - 140 315 490
GRMZM2G088235_P01 5 83860797 - 83865920 - 141 316 491
GRMZ8620088235_PO4 5 83861394 - 83865914 - 142 317 492
GRMZM2G088235 PO5 5 83864692 - 83865653 - 143 318 493
GRMZI9E2G387123J01 5 83867332- 83868010 - 144 319 494
GRMZM2G449843_PO1 5 84018779 - 84019752 + 145 320 495
GRMZM26322129 P01 5 84061561 -84065912 + 146 321 496
GRIMZ1V12G017741_P01 5 84083388 - 84086632 + 147 322 497
GRMZM213017802 P01 5 84088707 - 84089603 - 148 323 498
GRMZM20074634_P05 5 84101452 - 84104814 - 149 324 499
GRMLM2(3074634_P0 1 5 84101452 - 84105175 - 150 325 500
G1tMZM20074634 PO2 5 84101452 - 84105175 - 151 326 501
GRMZM2G074634 PO4 5 84101452 - 84105175 - 152 327 502
GRMZM2G074634 PO3 5 84101452 - 84105175 - 153 328 503
GRM1M20074634_P06 5 84103364 - 84105175 - 154 329 504
GRMZM20026117_P02 5 84248220 - 84251635 '-= 155 330 505
GRMZM2G026117_PO1 5 84248220 - 84252180 -, 156 331 506
0R54ZM20026117 PO3 5 84248224 - 84252180 4- 157 332 507
GR1v1ZM2G005998 PO2 5 84252053 - 84253030 - 158 333 508
GRMZM2G005998 PO3 5 84252053 - 84254208 - 159 334 509
GRMZM2G005998_P01 5 84253581 - 84254208 - 160 335 510
GRMZM2G107026 P01 5 84314151 - 84314930 - 161 336 511
AC211514.2 FGP003 5 84338664 - 84340523 - 162 337 512
AC208217.3 FGP001 5 84516113 - 84516340 - 163 338 513
GR1V1ZM2G127999_P01 5 84706267 - 84706916 I 164 339 514
GRMZM2G128012_PO1 5 84796405 - 84799488 - 165 340 515
GRMZM2G427468 P01 5 84799805 - 84801081 - 166 341 516
GRMZM2G382914 PO5 5 84821810 - 84824816 + 167 342 517
GRMEM2G382914_PO4 5 84821810 - 84825422 + 168 343 518
GRMZM2G382914 PO2 5 84822183 - 84825763 + 169 344 519
GRMZM26382914_P03 5 84822215 - 84825763 + 170 345 520
G11MZM2G382914 P01 5 84822215 - 84825942 + 171 346 521
GRM/M2G007372_PO1 5 84840183 - 84843411 + 172 347 522
GRMZM2G010321 PO2 5 84934242 - 84936441 + 173 348 523
GRMZM2G010321_PO1 5 84934242 - 84936493 + 174 349 524
G11MZ1M2G010754 P01 5 84938287 - 84943705 - 175 350 525
The above examples clearly illustrate the advantages of the invention.
Although the
present invention has been described with reference to specific details of
certain
260
CA 02939580 2016-08-11
WO 2015/127248
PCT/US2015/016877
embodiments thereof, it is not intended that such details should be regarded
as limitations
upon the scope of the claimed invention except as and to the extent that they
are included in
the accompanying claims.
261
